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Research Papers

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A preliminary examination of how serotonergic polymorphisms influence brain response following an adolescent cannabis intervention

Authors: Sarah W.FeldsteinEwing, HilaryK.Mead, UmaYezhuvath, SamDeWitt, Kent E.Hutchison, FrancescaM.Filbey
Publication Date: October, 2012

Given the link between depression, anxiety, and cannabis abuse, a serotonin receptor (rs6311) and transporter polymorphism (rs2020936) were examined as moderators of neural response as measured by functional magnetic resonance imaging following a psychosocial treatment for cannabis use disorders (CUDs). While the proposed hypotheses were unsupported, we found that the rs6311 C allele was significantly related to brain activation (medial frontal gyrus, precuneus), indicating the role of this serotonin receptor in adolescent treatment response.

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Scopolamine and olfactory function

Authors: Serby M., Flicker C., Rypma B., Weber S., Rotrosen J.P., Ferris S.H.
Publication Date: May, 1989

Brief Report

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Load-dependent roles of frontal brain regions in the maintenance of working memory

Authors: Rypma B., Prabhakaran V., Desmond J.E., Glover G.H., Gabrieli J.D.E.
Publication Date: December, 1997

Brain imaging studies have suggested a critical role for prefrontal cortex in working memory (WM) tasks that require both maintainenance and manipulation of information over time in delayed-responseWMtasks. In the present study, functional magnetic resonance imaging (fMRI) was used to examine whether prefrontal areas are activated when only maintenance is required in a delayed-response WM task, without the overt requirement to manipulate the stored information. In two scans, six subjects performed WM tasks in which, on each trial, they (1) encoded 1, 3, or 6 to-beremembered letters, (2) maintained these letters across a 5-second unfilled delay, and (3) determined whether a single probe letter was or was not part of the memory set. Activation of left caudal inferior frontal gyrus was observed, relative to the 1-letter task, when subjects were required to maintain 3 letters in WM. When subjects were required to maintain 6 letters in WM, additional prefrontal areas, most notably middle and superior frontal gyri, were activated bilaterally. Thus, increasing the amount of to-be-maintained information, without any overt manipulation requirement, resulted in the recruitment of wide-spread frontallobe regions. Inferior frontal gyrus activation was left-hemisphere dominant in both the 3- and 6-letter conditions, suggesting that such activation reflected material-specific verbal processes. Activation in middle and superior frontal gyri appeared only in the 6-letter condition and was right-hemisphere dominant, suggesting that such activation reflected material-independent executive processes.

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The roles of prefrontal brain regions in components of working memory: Effects of memory load and individual differences

Authors: Rypma B., D'Esposito M.
Publication Date: October, 1998

Using an event-related functional MRI design, we explored the relative roles of dorsal and ventral prefrontal cortex (PFC) regions during specific components (Encoding, Delay, Response) of a working memory task under different memory-load conditions. In a group analysis, effects of increased memory load were observed only in dorsal PFC in the encoding period. Activity was lateralized to the right hemisphere in the high but not the low memory-load condition. Individual analyses revealed variability in activation patterns across subjects. Regression analyses indicated that one source of variability was subjects’ memory retrieval rate. It was observed that dorsal PFC plays a differentially greater role in information retrieval for slower subjects, possibly because of inefficient retrieval processes or a reduced quality of mnemonic representations. This study supports the idea that dorsal and ventral PFC play different roles in component processes of working memory.

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The effect of normal aging on the coupling of neural activity to the bold hemodynamic response

Authors: D'Esposito M., Zarahn E., Aguirre G.K., Rypma B.
Publication Date: September, 1998

The use of functional neuroimaging to test hypotheses regarding age-related changes in the neural substrates of cognitive processes relies on assumptions regarding the coupling of neural activity to neuroimaging signal. Differences in neuroimaging signal response between young and elderly subjects can be mapped directly to differences in neural response only if such coupling does not change with age. Here we examined spatial and temporal characteristics of the BOLD fMRI hemodynamic response in primary sensorimotor cortex in young and elderly subjects during the performance of a simple reaction time task. We found that 75% of elderly subjects (n 5 20) exhibited a detectable voxel-wise relationship with the behavioral paradigm in this region as compared to 100% young subjects (n 5 32). The median number of suprathreshold voxels in the young subjects was greater than four times that of the elderly subjects. Young subjects had a slightly greater signal:noise per voxel than the elderly subjects that was attributed to a greater level of noise per voxel in the elderly subjects. The evidence did not support the idea that the greater head motion observed in the elderly was the cause of this greater voxel-wise noise. There were no significant differences between groups in either the shape of the hemodynamic response or in its the within-group variability, although the former evidenced a near significant trend. The overall finding that some aspects of the hemodynamic coupling between neural activity and BOLD fMRI signal change with age cautions against simple interpretations of the results of imaging studies that compare young and elderly subjects. Key Words: functional MRI; aging; BOLD; hemodynamic response

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Imagined transformations of bodies: An fMRI investigation

Authors: Zacks J., Rypma B., Gabrieli J.D.E., Tversky B., Glover G.H.
Publication Date: November, 1998

A number of spatial reasoning problems can be solved by performing an imagined transformation of one's egocentric perspective. A series of experiments were carried out to characterize this process behaviorally and in terms of its brain basis, using functional magnetic resonance imaging (fMRI). In a task contrast designed to isolate egocentric perspective transformations, participants were slower to make left-right judgments about a human ®gure from the ®gure's perspective than from their own. This transformation led to increased cortical activity around the left parietal-temporal-occipital junction, as well as in other areas including left frontal cortex. In a second task contrast comparing judgments about inverted ®gures to judgments about upright ®gures (always from the ®gure's perspective), participants were slower to make left-right judgments about inverted ®gures than upright ones. This transformation led to activation in posterior areas near those active in the ®rst experiment, but weaker in the left hemisphere and stronger in the right, and also to substantial left frontal activation. Together, the data support the specialization of areas near the parietal-temporal-occipital junction for egocentric perspective transformations. These results are also suggestive of a dissociation between egocentric perspective transformations and object- based spatial transformations such as mental rotation. Keywords: Mental rotation; fMRI; Egocentric; Spatial; Perspective

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Isolating the neural mechanisms of age-related changes in human working memory

Authors: Rypma B., D'Esposito M.
Publication Date: March, 2000

Working memory (WM), the process by which information is coded into memory, actively maintained and subsequently retrieved, declines with age. To test the hypothesis that age-related changes in prefrontal cortex (PFC) may mediate this WM decline, we used functional MRI to investigate age differences in PFC activity during separate WM task components (encoding, maintenance, retrieval). We found greater PFC activity in younger than older adults only in dorsolateral PFC during memory retrieval. Fast younger subjects showed less dorsolateral PFC activation during retrieval than slow younger subjects, whereas older adults showed the opposite pattern. Thus age-related changes in dorsolateral PFC and not ventrolateral PFC account for WM decline with normal aging.

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Functional neuroimaging of short-term memory: The neural mechanisms of mental storage

Authors: Rypma B., Gabrieli J.D.E.
Publication Date: January, 2000

Cowan argues that the true short-term memory (STM) capacity limit is about 4 items. Functional neuroimaging data converge with this conclusion, indicating distinct neural activity patterns depending on whether or not memory task-demands exceed this limit. STM for verbal information within that capacity invokes focal prefrontal cortical activation that increases with memory load. STM for verbal information exceeding that capacity invokes widespread prefrontal activation in regions associated with executive and attentional processes that may mediate chunking processes to accommodate STM capacity limits. Page 57

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A subsequent-memory effect in dorsolateral prefrontal cortex

Authors: Rypma B., D'Esposito M.
Publication Date: September, 2002

The importance of brain regions for long-term memory encoding has been examined by comparison of encoding-related neural activity on trials in which successful recollection subsequently occurred to the encoding-related activity on trials in which successful recollection did not occur. We applied similar analyses to event-related functional magnetic resonance imaging (fMRI) data to explore the relative roles of dorsolateral and ventrolateral prefrontal cortex (PFC) regions during specific components of a working-memory (WM) maintenance task. The results of this study indicated that increases in dorsolateral PFC activity during encoding was related to subsequent retrieval-success. These results lend support to the hypothesis that ventrolateral PFC mediates a limited-capacity WM buffer that supports rehearsal maintenance functions while dorsolateral PFC mediates WM organization functions that accommodate the capacity limits of WM maintenance. Keywords: Working memory; Prefrontal cortex; Functional magnetic resonance imaging; Subsequent-memory effect

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Factors controlling neural activity during delayed-response task performance: Testing a memory organization hypothesis of prefrontal function

Authors: Rypma B.
Publication Date: December, 2005

Understanding the role of prefrontal cortex in delayed- response task performance has been a central focus of neuroimaging research. The first part of this review will emphasize consistent observations of memory-load-related effects on prefrontal cortex activity that have led me and my colleagues to propose a “memory-organization hypothesis” of prefrontal cortex function. The second part examines how predictions of this hypothesis have borne up to empirical testing. The final part of this review suggests that there is important information contained in between-study variance in the anatomical locus and temporal sequence of neural activity. I will examine how subtle variations in task-structure affect subjects’ strategies, producing meaningful variability in neuroimaging data. Systematic manipulation of these variables in future research can assist in elucidating the role of prefrontal cortex in delayed response task performance. Key words: working memory, delayed-response task, prefrontal cortex, functional neuroimaging.

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Prefrontal modulation of working memory performance in brain injury and disease

Authors: Hillary F.G., Genova H.M., Chiaravalloti N.D., Rypma B., DeLuca J.
Publication Date: January, 2006

The inter-related cognitive constructs of working memory (WM) and processing speed are fundamental components to general intellectual functioning in humans. Importantly, both WM and processing speed are highly susceptible to disruption in cases of brain injury, neurologic illness, and even in normal aging. A goal of this article is to summarize and critique the functional imaging studies of speeded working memory in neurologically impaired populations. This review focuses specifically on the role of the lateral prefrontal cortex in mediating WM performance and integrates the relevant WM literature in healthy adults with the current findings in the clinical literature. One important finding emerging from a summary of this literature is the dissociable contributions made by ventrolateral and dorsolateral prefrontal cortex (VLPFC and DLPFC) in guiding performance on tasks of WM. Throughout this review, it is shown that when cerebral resources are challenged, it is DLPFC, and often right DLPFC specifically, that plays a critical role in modulating WM functioning. In addition, this article will examine the relationship between task performance and brain activation across studies to clarify the role of increased DLPFC activity in clinical samples. Finally, explanations are offered for the observed increased DLPFC activation and the potentially unique role of right DLPFC in mediating WM performance during periods of cerebral challenge. Key words: functional imaging; prefrontal cortex; working memory; TBI; MS; brain injury

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Neural correlates of cognitive efficiency

Authors: Rypma B., Berger J.S., Prabhakaran V., Martin Bly B., Kimberg D.Y., Biswal B.B., D'Esposito M.
Publication Date: September, 2006

Since its inception, experimental psychology has sought to account for individual differences in human performance. Some neuroimaging research, involving complex behavioral paradigms, has suggested that faster-performing individuals show greater neural activity than slower performers. Other research has suggested that faster-performing individuals show less neural activity than slower performers. To examine the neural basis of individual performance differences, we had participants perform a simple speeded-processing task during fMRI scanning. In some prefrontal cortical (PFC) brain regions, faster performers showed less cortical activity than slower performers while in other PFC and parietal regions they showed greater activity. Regional-causality analysis indicated that PFC exerted more influence over other brain regions for slower than for faster individuals. These results suggest that a critical determinant of individual performance differences is the efficiency of interactions between brain regions and that slower individuals may require more prefrontal executive control than faster individuals to perform successfully. Keywords: Human brain; Functional MRI; Cognitive control; Executive control

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Evidence for multiple manipulation processes in prefrontal cortex

Authors: Eldreth D.A., Patterson M.D., Porcelli A.J., Biswal B.B., Rebbechi D., Rypma B.
Publication Date: October, 2006

The prefrontal cortex (PFC) is known to subserve working memory (WM) processes. Brain imaging studies of WM using delayed response tasks (DRTs) have shown memory-loaddependent activation increases in dorsal prefrontal cortex (PFC) regions. These activation increases are believed to reflect manipulation of to-be-remembered information in the service of memory-consolidation. This speculation has been based on observations of similar activation increases in tasks that overtly require manipulation by instructing participants to reorder to-be-remembered list items. In this study, we tested the assumption of functional equivalence between these two types of WM tasks. Participants performed a DRT under two conditions with memory loads ranging from 3 to 6 letters. In an “item-order” condition, participants were required to remember letters in the order in which they were presented. In a “reordering” condition, participants were required to remember the letters in alphabetical order. Load-related activation increases were observed during the encoding and maintenance periods of the order maintenance condition, whereas load-related activation decreases were observed in the same periods of the reordering condition. These results suggest that (1) the neural substrates associated with long-list retention and those associated with reordering are not equivalent, (2) cognitive processes associated with long-list retention may be more closely approximated by item-order maintenance than by reordering, and (3) multiple forms of WM manipulation are dissociable on the basis of fMRI data.

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Age-related differences in activation-performance relations in delayed-response tasks: A multiple component analysis

Authors: Rypma B., Eldreth D.A., Rebbechi D.
Publication Date: February, 2006

We used event-related functional magnetic resonance imaging (fMRI) to measure prefrontal cortex (PFC) activity while younger and older adults performed an item-recognition task in which the memory-set size varied between 1 and 8 letters. Each trial was composed of a 4-sec encoding period in which subjects viewed random letter strings, a 12-sec retention period and a 2-sec retrieval period in which subjects decided whether a single probe letter was or was not part of the memory set. For both groups, reaction-time (RT) increased and accuracy decreased with increasing memory set-size. Analyses of individual subjects’ performance and cortical activity indicated that speed and accuracy accounted for variance in different task periods in dorsal and ventral PFC. Age-related differences in accuracy-activation relations were observed in dorsal PFC during encoding and ventral PFC during maintenance. Age-related differences in RT-activation relations were observed in dorsal PFC during retrieval. These results and additional fMRI data we have collected during performance of a speeded processing task, directly support a model of cognitive slowing in which processing rate is related to neural efficiency. Key words: prefrontal cortex, working memory, aging, individual differences, fMRI

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P-FIT and the neuroscience of intelligence: How well does P fit?

Authors: Prabhakaran V., Rypma B.
Publication Date: January, 2007

A well-recognized framework for modeling human intelligence centers around Spearman’s g, a common central factor accounting for individual differences in cognitive performance across a variety of complex tasks (Spearman 1904). The neural basis of g may be better characterized by posterior-frontal integration, rather than parietal, which may be just one of many posterior regions that are controlled by the prefrontal cortex (PFC). Page 32

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Hemodynamic scaling of fMRI-BOLD signal: validation of low-frequency spectral amplitude as a scalability factor

Authors: Biswal B.B., Kannurpatti S.S., Rypma B.
Publication Date: March, 2007

Functional magnetic resonance imaging blood-oxygenation-level-dependent (fMRI-BOLD) signal representing neural activity may be optimized by discriminating MR signal components related to neural activity and those related to intrinsic properties of the cortical vasculature. The objective of this study was to reduce the hemodynamic change independent of neural activity to obtain a scaled fMRIBOLD response using two factors, namely, low-frequency spectral amplitude (LFSA) and breath-hold amplitude (BHA). Ten subjects (age range, 22–38 years) were scanned during four task conditions: (a) rest while breathing room air, (b) bilateral finger tapping while breathing room air, (c) rest during a four inspirational breath-hold, and (d) rest during moderate hypercapnia (breathing 5% CO2, 20% O2 and 75% N2). In all subjects who breathed 5% CO2, regions with significant BOLD response during breath-hold correlated significantly with the percent signal increase during 5% CO2 inhalation. Finger-tapping-induced responses in the motor cortex were diminished to a similar extent after scaling using either LFSA or BHA. Inter- and intrasubject variation in the amplitude of the BOLD signal response reduced after hemodynamic scaling using LFSA or BHA. The results validated the hemodynamic amplitude scaling using LFSA with the earlier established BHA. LFSA free from motor-task contamination can be used to calibrate the fMRI-BOLD response in lieu of BHA or hypercapnia to minimize intra- and intersubject variation arising from vascular anatomy and vasodilative capacity. Keywords: fMRI; Breath-hold; BOLD; CBF; Scaling; Hypercapnia; Low frequency; Spectral amplitude

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The effects of acute stress on human prefrontal working memory systems

Authors: Porcelli A.J., Cruz D., Wenberg K., Patterson M.D., Biswal B.B., Rypma B.
Publication Date: April, 2008

We examined the relationship between acute stress and prefrontal-cortex (PFC) based working memory (WM) systems using behavioral (Experiment 1) and functional magnetic resonance imaging (fMRI; Experiment 2) paradigms. Subjects performed a delayed-response item-recognition task, with alternating blocks of high and low WM demand trials. During scanning, participants performed this task under three stress conditions: cold stress (induced by cold-water hand-immersion), a room temperature water control (induced by tepid-water hand-immersion), and no-water control (no hand-immersion). Performance was affected by WM demand, but not stress. Cold stress elicited greater salivary cortisol readings in behavioral subjects, and greater PFC signal change in fMRI subjects, than control conditions. These results suggest that, under stress, increases in PFC activity may be necessary to mediate cognitive processes that maintain behavioral organization.

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When less is more and when more is more: The mediating roles of capacity and speed in brain-behavior efficiency

Authors: Rypma B., Prabhakaran V.
Publication Date: January, 2009

An enduring enterprise of experimental psychology has been to account for individual differences in human performance. Recent advances in neuroimaging have permitted testing of hypotheses regarding the neural bases of individual differences but this burgeoning literature has been characterized by inconsistent results. We argue that careful design and analysis of neuroimaging studies is required to separate individual differences in processing capacity from individual differences in processing speed to account for these differences in the literature.We utilized task designs which permitted separation of processing capacity influences on brainbehavior relationships from those related to processing speed. In one set of studies, participants performed verbal delayed-recognition tasks during blocked and event-related fMRI scanning. The results indicated that those participants with greater working memory (WM) capacity showed greater prefrontal cortical activity, strategically capitalized on the additional processing time available in the delay period, and evinced faster WM-retrieval rates than low-capacity participants. In another study, participants performed a digit-symbol substitution task (DSST) designed to minimize WM storage capacity requirements and maximize processing speed requirements during fMRI scanning. In some prefrontal cortical (PFC) brain regions, participants with faster processing speed showed less PFC activity than slower performers while in other PFC and parietal regions they showed greater activity. Regional-causality analysis indicated that PFC exerted more influence over other brain regions for slower than for faster individuals. These results support a model of neural efficiency in which individuals differ in the extent of direct processing links between neural nodes. One benefit of direct processing links may be a surplus of resources that maximize available capacity permitting fast and accurate performance.

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Examination of processing speed deficits in multiple sclerosis using functional magnetic resonance imaging

Authors: Genova H.M., Hillary F.G., Wylie G., Rypma B., Deluca J.
Publication Date: January, 2009

Although it is known that processing speed defi cits are one of the primary cognitive impairments in multiple sclerosis (MS), the underlying neural mechanisms responsible for impaired processing speed remain undetermined. Using BOLD functional magnetic resonance imaging, the current study compared the brain activity of 16 individuals with MS to 17 healthy controls (HCs) during performance of a processing speed task, a modifi ed version of the Symbol Digit Modalities Task. Although there were no differences in performance accuracy, the MS group was signifi cantly slower than HCs. Although both groups showed similar activation involving the precentral gyrus and occipital cortex, the MS showed signifi cantly less cerebral activity than HCs in bilateral frontal and parietal regions, similar to what has been reported in aging samples during speeded tasks. In the HC group, processing speed was mediated by frontal and parietal regions, as well as the cerebellum and thalamus. In the MS group, processing speed was mediated by insula, thalamus and anterior cingulate. It therefore appears that neural networks involved in processing speed differ between MS and HCs, and our fi ndings are similar to what has been reported in aging, where damage to both white and gray matter is linked to processing speed impairments. Keywords : Multiple sclerosis , Processing speed , fMRI , Symbol Digit Modalities Task , Brain mapping , Cognition

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Working memory component processes: Isolating BOLD signal changes

Authors: Motes M.A., Rypma B.
Publication Date: September, 2009

The chronology of the component processes subserving working memory (WM) and hemodynamic response lags has hindered the use of fMRI for exploring neural substrates of WM. In the present study, however, participants completed full trials that involved encoding two or six letters, maintaining the memory set over a delay, and then deciding whether a probe was in the memory set or not. Additionally, they completed encode-only, encode-and-maintain, and encode-and-decide partial trials intermixed with the full trials. The inclusion of partial trials allowed for the isolation of BOLD signal changes to the different trial periods. The results showed that only lateral and medial prefrontal cortex regions differentially responded to the 2- and 6-letter memory sets over the trial periods, showing greater activation to 6-letter sets during the encode and maintain trial periods. Thus, the data showed the differential involvement of PFC in the encoding and maintenance of supra- and sub-capacity memory sets and show the efficacy of using fMRI partial trial methods to study WM component processes.

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Toward discovery science of human brain function

Authors: Biswal B.B., Mennes M., Zuo X.-N., Gohel S., Kelly C., Smith S.M., Beckmann C.F., Adelstein J.S., Buckner R.L., Colcombe S., Dogonowski A.-M., Ernst M., Fair D., Hampson M., Hoptman M.J., Hyde J.S., Kiviniemi V.J., Kotter R., Li S.-J., Lin C.-P., Lowe M.J., Mackay C., Madden D.J., Madsen K.H., Margulies D.S., Mayberg H.S., McMahon K., Monk C.S., Mostofsky S.H., Nagel B.J., Pekar J.J., Peltier S.J., Petersen S.E., Riedl V., Rombouts S.A.R.B., Rypma B., Schlaggar B.L., Schmidt S., Seidler R.D., Siegle G.J., S
Publication Date: March, 2010

Although it is being successfully implemented for exploration of the genome, discovery science has eluded the functional neuroimaging community. The core challenge remains the development of common paradigms for interrogating the myriad functional systems in the brain without the constraints of a priori hypotheses. Resting-state functional MRI (R-fMRI) constitutes a candidate approach capable of addressing this challenge. Imaging the brain during rest reveals large-amplitude spontaneous low-frequency (<0.1 Hz) fluctuations in the fMRI signal that are temporally correlated across functionally related areas. Referred to as functional connectivity, these correlations yield detailed maps of complex neural systems, collectively constituting an individual’s “functional connectome.” Reproducibility across datasets and individuals suggests the functional connectome has a common architecture, yet each individual’s functional connectome exhibits unique features, with stable, meaningful interindividual differences in connectivity patterns and strengths. Comprehensive mapping of the functional connectome, and its subsequent exploitation to discern genetic influences and brain–behavior relationships, will require multicenter collaborative datasets. Here we initiate this endeavor by gathering R-fMRI data from 1,414 volunteers collected independently at 35 international centers. We demonstrate a universal architecture of positive and negative functional connections, as well as consistent loci of inter-individual variability. Age and sex emerged as significant determinants. These results demonstrate that independent R-fMRI datasets can be aggregated and shared. Highthroughput R-fMRI can provide quantitative phenotypes for molecular genetic studies and biomarkers of developmental and pathological processes in the brain. To initiate discovery science of brain function, the 1000 Functional Connectomes Project dataset is freely accessible at www.nitrc.org/projects/fcon_1000/.

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Neural and vascular variability and the fMRI-BOLD response in normal aging

Authors: Kannurpatti S.S., Motes M.A., Rypma B., Biswal B.B.
Publication Date: December, 2009

Neural, vascular and structural variables contributing to the blood oxygen level-dependent (BOLD) signal response variability were investigated in younger and older humans. Twelve younger healthy human subjects (six male and six female; mean age: 24 years; range: 19– 27 years) and 12 older healthy subjects (five male and seven female; mean age: 58 years; range: 55–71 years) with no history of head trauma and neurological disease were scanned. Functional magnetic resonance imaging measurements using the BOLD contrast were made when participants performed a motor, cognitive or a breath hold (BH) task. Activation volume and the BOLD response amplitude were estimated for the younger and older at both group and subject levels. Mean activation volume was reduced by 45%, 40% and 38% in the elderly group during the motor, cognitive and BH tasks, respectively, compared to the younger. Reduction in activation volume was substantially higher compared to the reduction in the gray matter volume of 14% in the older compared to the younger. A significantly larger variability in the intersubject BOLD signal change occurred during the motor task, compared to the cognitive task. BH-induced BOLD signal change between subjects was significantly less-variable in the motor task-activated areas in the younger compared to older whereas such a difference between age groups was not observed during the cognitive task. Hemodynamic scaling using the BH signal substantially reduced the BOLD signal variability during the motor task compared to the cognitive task. The results indicate that the origin of the BOLD signal variability between subjects was predominantly vascular during the motor task while being principally a consequence of neural variability during the cognitive task. Thus, in addition to gray matter differences, the type of task performed can have different vascular variability weighting that can influence age-related differences in brain functional response. Keywords: f MRI; Breath hold; BOLD; CBF; Hypercapnia; Variability; Motor; Cognitive; Neural; Vascular

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Task-dependent individual differences in prefrontal connectivity

Authors: Biswal B.B., Eldreth D.A., Motes M.A., Rypma B.
Publication Date: January, 2010

Recent advances in neuroimaging have permitted testing of hypotheses regarding the neural bases of individual differences, but this burgeoning literature has been characterized by inconsistent results. To test the hypothesis that differences in task demands could contribute to between-study variability in brain-behavior relationships, we had participants perform 2 tasks that varied in the extent of cognitive involvement. We examined connectivity between brain regions during a low-demand vigilance task and a higher-demand digit--symbol visual search task using Granger causality analysis (GCA). Our results showed 1) Significant differences in numbers of frontoparietal connections between low- and high-demand tasks 2) that GCA can detect activity changes that correspond with task-demand changes, and 3) faster participants showed more vigilance-related activity than slower participants, but less visual-search activity. These results suggest that relatively low-demand cognitive performance depends on spontaneous bidirectionally fluctuating network activity, whereas high-demand performance depends on a limited, unidirectional network. The nature of brain-behavior relationships may vary depending on the extent of cognitive demand. High-demand network activity may reflect the extent to which individuals require top-down executive guidance of behavior for successful task performance. Low-demand network activity may reflect task- and performance monitoring that minimizes executive requirements for guidance of behavior. Keywords: connectivity, functional imaging, individual differences, prefrontal cortex, processing speed

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Non-neural BOLD variability in block and event-related paradigms

Authors: Kannurpatti S.S., Motes M.A., Rypma B., Biswal B.B.
Publication Date: July, 2010

Block and event-related stimulus designs are typically used in fMRI studies depending on the importance of detection power or estimation efficiency. The extent of vascular contribution to variability in block and event-related fMRI-BOLD response is not known. With scaling, the extent of vascular variability in the fMRI-BOLD response during block and event-related design tasks was investigated. Blood oxygen leveldependent (BOLD) contrast data from healthy volunteers performing a block design motor task and an event-related memory task requiring performance of a motor response were analyzed from the regions of interest (ROIs) surrounding the primary and supplementary motor cortices. Average BOLD signal change was significantly larger during the block design compared to the event-related design. In each subject, BOLD signal change across voxels in the ROIs had higher variation during the block design task compared to the event-related design task. Scaling using the resting state fluctuation of amplitude (RSFA) and breath-hold (BH), which minimizes BOLD variation due to vascular origins, reduced the within-subject BOLD variability in every subject during both tasks but significantly reduced BOLD variability across subjects only during the block design task. The strong non-neural source of intra- and intersubject variability of BOLD response during the block design compared to event-related task indicates that study designs optimizing for statistical power through enhancement of the BOLD contrast (for, e.g., block design) can be affected by enhancement of non-neural sources of BOLD variability. Keywords: Breath-hold; Block design; Event related; fMRI; Hypercapnia; Vascular; Motor cortex; Scaling; Resting state

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Age-dependent relationships between prefrontal cortex activation and processing efficiency

Authors: Motes A.A., Biswal B.B., Rypma B.
Publication Date: October, 2010

Functional magnetic resonance imaging (fMRI) was used in the present study to examine the neural basis for agerelated differences in processing efficiency, particularly targeting prefrontal cortex (PFC). During scanning, older and younger participants completed a processing efficiency task in which they determined on each trial whether a symbol–number pair appeared in a simultaneously presented array of nine symbol–number pairs. Estimates of task-related blood-oxygen-level-dependent (BOLD) signal-change were obtained for each participant. These estimates were then correlated with the participants’ performance on the task. For younger participants, BOLD signalchange within PFC decreased with better performance, but for older participants, BOLD signal-change within PFC increased with better performance. The results support the hypothesis that the availability and use of PFC resources mediate age-related changes in processing efficiency. Keywords: Processing efficiency; Individual differences; Cognitive aging; Prefrontal cortex; Neuroimaging.

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Increasing measurement accuracy of age-related BOLD signal change: Minimizing vascular contributions by resting-state-fluctuation-of-amplitude scaling

Authors: Kannurpatti S.S., Motes M.A., Rypma B., Biswal B.B.
Publication Date: July, 2010

In this report we demonstrate a hemodynamic scaling method with resting-state fluctuation of amplitude (RSFA) in healthy adult younger and older subject groups. We show that RSFA correlated with breath hold (BH) responses throughout the brain in groups of younger and older subjects which RSFA and BH performed comparably in accounting for age-related hemodynamic coupling changes, and yielded more veridical estimates of age-related differences in task-related neural activity. BOLD data from younger and older adults performing motor and cognitive tasks were scaled using RSFA and BH related signal changes. Scaling with RSFA and BH reduced the skew of the BOLD response amplitude distribution in each subject and reduced mean BOLD amplitude and variability in both age groups. Statistically significant differences in intrasubject amplitude variation across regions of activated cortex, and intersubject amplitude variation in regions of activated cortex were observed between younger and older subject groups. Intra- and intersubject variability differences were mitigated after scaling. RSFA, though similar to BH in minimizing skew in the unscaled BOLD amplitude distribution, attenuated the neural activity-related BOLD amplitude significantly less than BH. The amplitude and spatial extent of group activation were lower in the older than in the younger group before and after scaling. After accounting for vascular variability differences through scaling, age-related decreases in activation volume were observed during the motor and cognitive tasks. The results suggest that RSFA-scaled data yield agerelated neural activity differences during task performance with negligible effects from non-neural (i.e., vascular) sources.

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Capacity-speed relationships in prefrontal cortex

Authors: Prabhakaran V., Rypma B., Narayanan N.S., Meier T.B., Austin B.P., Nair V.A., Naing L., Thomas L.E., Gabrieli J.D.E.
Publication Date: November, 2012

Working memory (WM) capacity and WM processing speed are simple cognitive measures that underlie human performance in complex processes such as reasoning and language comprehension. These cognitive measures have shown to be interrelated in behavioral studies, yet the neural mechanism behind this interdependence has not been elucidated. We have carried out two functional MRI studies to separately identify brain regions involved in capacity and speed. Experiment 1, using a block-design WM verbal task, identified increased WM capacity with increased activity in right prefrontal regions, and Experiment 2, using a single-trial WM verbal task, identified increased WM processing speed with increased activity in similar regions. Our results suggest that right prefrontal areas may be a common region interlinking these two cognitive measures. Moreover, an overlap analysis with regions associated with binding or chunking suggest that this strategic memory consolidation process may be the mechanism interlinking WM capacity and WM speed.

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Prediction of task-related BOLD fMRI with amplitude signatures of resting-state fMRI

Authors: Kannurpatti S.S., Rypma B., Biswal B.B.
Publication Date: March, 2012

Blood oxygen contrast-functional magnetic resonance imaging (fMRI) signals are a convolution of neural and vascular components. Several studies indicate that task-related (T-fMRI) or resting-state (R-fMRI) responses linearly relate to hypercapnic task responses. Based on the linearity of R-fMRI and T-fMRI with hypercapnia demonstrated by different groups using different study designs, we hypothesized that R-fMRI and T-fMRI signals are governed by a common physiological mechanism and that resting-state fluctuation of amplitude (RSFA) should be linearly related to T-fMRI responses. We tested this prediction in a group of healthy younger humans where R-fMRI, T-fMRI, and hypercapnic (breath hold, BH) task measures were obtained form the same scan session during resting state and during performance of motor and BH tasks. Within individual subjects, significant linear correlations were observed between motor and BH task responses across voxels. When averaged over the whole brain, the subject-wise correlation between the motor and BH tasks showed a similar linear relationship within the group. Likewise, a significant linear correlation was observed between motor-task activity and RSFA across voxels and subjects. The linear rest–task (R–T) relationship between motor activity and RSFA suggested that R-fMRI and T-fMRI responses are governed by similar physiological mechanisms. A practical use of the R–T relationship is its potential to estimate T-fMRI responses in special populations unable to perform tasks during fMRI scanning. Using the R–T relationship determined from the first group of 12 healthy subjects, we predicted the T-fMRI responses in a second group of 7 healthy subjects. RSFA in both the lower and higher frequency ranges robustly predicted the magnitude of T-fMRI responses at the subject and voxel levels. We propose that T-fMRI responses are reliably predictable to the voxel level in situations where only R-fMRI measures are possible, and may be useful for assessing neural activity in task non-compliant clinical populations.

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Calibrating BOLD fMRI activations with neurovascular and anatomical constraints

Authors: Di X., Kannurpatti S.S., Rypma B., Biswal B.B.
Publication Date: February, 2012

Functional magnetic resonance imaging signals, in addition to reflecting neuronal response, also contain physiological variances. These factors may introduce variability into blood oxygen level-- dependent (BOLD) activation results, particularly in different population groups. In this study, we hypothesized that the amplitude as well as the spatial extent of BOLD activation could be improved after minimizing the variance caused by the neurovascular and anatomical factors. Subjects were scanned while they performed finger tapping and digit-symbol substitution tasks (DSSTs). Partial volume and neurovascular effects were estimated on a voxelwise basis using subjects’ own gray matter volume (GMV), breath holding (BH), and amplitude of low-frequency fluctuation (ALFF). The results showed that all individual’s GMV, BH, and ALFF could significantly predict motor and DSST activations in a voxelwise manner. Wholebrain analyses were conducted to regress out the anatomical and neurovascular information. Differential maps (obtained using t-test) indicated that the adjustment tended to suppress activation in regions that were near vessels such as midline cingulate gyrus, bilateral anterior insula, and posterior cerebellum. These results suggest that voxelwise adjustment using GMV and neurovascular parameters can minimize structural and physiological variances among individuals and be used for quantitative comparisons. Keywords: BOLD, breath hold, calibration, cognition, fMRI, hypercapnic scaling, motor, resting-state

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Is the Concreteness Effect a Result of Underlying Network Interconnectivity?

Authors: Gee N.R., Nelson D.L., Krawczyk D.
Publication Date: November, 1998

Two general classifications of theoretical explanations for concreteness effects are evaluated. Process theories are those that emphasize the nature of the processing initiated by the study items, and structural explanations are those that emphasize the role of long-term memory representations of the study items. A series of four experiments is presented in which structural variables such as the number of associates a word has in long-term memory (set size) and the density of the connections among those associates (connectivity) are crossed with concreteness under several different instructional manipulations in the cued recall task. The results consistently demonstrate that concreteness effects and effects related to the associative structure of the study items are not dependent upon one another, but instead have additive effects on performance. The results allow for the elimination of the structural explanations, in favor of one of the process theories: dual code theory. The results are also consistent with the overall framework of memory proposed by the PIER model.

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Contributions of the prefrontal cortex to the neural basis of human decision making

Authors: Krawczyk D.C.
Publication Date: June, 2002

The neural basis of decision making has been an elusive concept largely due to the many subprocesses associated with it. Recent efforts involving neuroimaging, neuropsychological studies, and animal work indicate that the prefrontal cortex plays a central role in several of these subprocesses. The frontal lobes are involved in tasks ranging from making binary choices to making multi-attribute decisions that require explicit deliberation and integration of diverse sources of information. In categorizing different aspects of decision making, a division of the prefrontal cortex into three primary regions is proposed. (1) The orbitofrontal and ventromedial areas are most relevant to deciding based on reward values and contribute affective information regarding decision attributes and options. (2) Dorsolateral prefrontal cortex is critical in making decisions that call for the consideration of multiple sources of information, and may recruit separable areas when making well defined versus poorly defined decisions. (3) The anterior and ventral cingulate cortex appear especially relevant in sorting among conflicting options, as well as signaling outcome-relevant information. This topic is broadly relevant to cognitive neuroscience as a discipline, as it generally comprises several aspects of cognition and may involve numerous brain regions depending on the situation. The review concludes with a summary of how these regions may interact in deciding and possible future research directions for the field. q 2002 Elsevier Science Ltd. All rights reserved.

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A Neurocomputational Model of Analogical Reasoning and its Breakdown in Frontotemporal Lobar Degeneration

Authors: Morrison R.G., Krawczyk D.C., Holyoak K.J., Hummel J.E., Chow T.W., Miller B.L., Knowlton B.J.
Publication Date: April, 2004

Analogy is important for learning and discovery and is considered a core component of intelligence. We present a computational account of analogical reasoning that is compatible with data we have collected from patients with cortical degeneration of either their frontal or anterior temporal cortices due to frontotemporal lobar degeneration (FTLD). These two patient groups showed different deficits in picture and verbal analogies: frontal lobe FTLD patients tended to make errors due to impairments in working memory and inhibitory abilities, whereas temporal lobe FTLD patients tended to make errors due to semantic memory loss. Using the ‘‘Learning and Inference with Schemas and Analogies’’ model, we provide a specific account of how such deficits may arise within neural networks supporting analogical problem solving.

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Construction of preferences by constraint satisfaction

Authors: Simon D., Krawczyk D.C., Holyoak K.J.
Publication Date: February, 2003

Participants were given a choice between two multiattribute alternatives (job offers). Preferences for the attributes were measured before, during, and after the choices were made. We found that over the course of decision making, the preferences shifted to cohere with the choice: The attributes of the option that was eventually chosen came to be rated more favorably than they had been rated initially, while the attributes of the rejected option received lower preference ratings than before. These coherence shifts were triggered by a single attribute that decisively favored one option (Experiment 1), and occurred spontaneously in the absence of a decisive attribute (Experiment 2). The coherence shift preceded commitment to choice. These findings favor constraint-satisfaction models of decision making.

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The one-to-one constraint in analogical mapping and inference

Authors: Krawczyk D.C., Holyoak K.J., Hummel J.E.
Publication Date: December, 2004

Theories of analogical reasoning have assumed that a 1-to-1 constraint discourages reasoners from mapping a single element in 1 analog to multiple elements in another. Empirical evidence suggests that reasoners sometimes appear to violate the 1-to-1 constraint when asked to generate mappings, yet virtually never violate it when asked to generate analogical inferences. However, few studies have examined analogical inferences based on nonisomorphic analogs, and their conclusions are suspect due to methodological problems. We sought to elicit mixed inferences that could result from combining information from 2 possible mappings. Participants generated 2-to-1 correspondences when asked for explicit mappings, but did not produce mixed inferences. Multiple correspondences appear to arise from multiple isomorphic mappings, rather than from a single homomorphic mapping.

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Reward modulation of prefrontal and visual association cortex during an incentive working memory task

Authors: Krawczyk D.C., Gazzaley A., D'Esposito M.
Publication Date: January, 2007

Cognitive performance differswith motivation, but little direct evidence exists regarding the neural mechanisms of the influence of reward motivation on working memory (WM). We tested the effects of motivation on the top-down control in visual WM. Encoding relevant stimuli for maintenance, while suppressing inappropriate inputs is considered a core process in cognition. Prior functional magnetic resonance imaging (fMRI) results demonstrated that stimulus-specific visual association cortex serves as a marker of activation differences for task-relevant and task-irrelevant inputs, such that enhanced activity occurs when attention is directed to relevant stimuli and suppressed activity occurs when attention is directed away from irrelevant stimuli [Gazzaley, A., Cooney, J., McEvoy, K., Knight, R.T., and D'Esposito,M. J. Cogn. Neurosci. 17, 507–517]. We used fMRI to test whether differential WM performance, indexed by lowered response times on a delayed-recognition task, was associated with amplification of enhancement and suppression effects during stimulus encoding within visual association cortex. Our results indicate that enhancement and suppression are amplified for trials with the highest reward level relative to nonrewarded trials for a scene-selective cortical region. In a face-selective region, similar modulation of enhancement for the highest reward level relative to non-rewarded trials was found. Prefrontal cortex also showed enhanced activity during high reward trials. Overall these results reveal that reward motivation can play a pivotal role in driving performance through top-down signaling in frontal regions involved in WM, as well as visual association regions selective to processing the perceptual inputs of the items to be remembered.

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The transience of constructed preferences

Authors: Simon D., Krawczyk D.C., Bleicher A., Holyoak K.J.
Publication Date: July, 2007

A large body of research suggests that preferences are constructed rather than merely accessed in the course of making decisions. The current research examines the stability of constructed preferences over time. Preferences for various factors relevant to a job choice were measured prior to presentation of the job-choice task, at the point of decision, and again following a delay. It was found that relative to baseline pre-decision levels, preferences shifted to provide stronger support for the emerging decision. Preference changes proved to be transient, receding to baseline after 1 week (Experiment 1), and even within 15 minutes (Experiment 2). These findings, which can be interpreted in terms of decision-making by constraint satisfaction, suggest that preferences are constructed to serve the decision at hand, without constraining the decision maker in future decisions.

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Distraction during relational reasoning: The role of prefrontal cortex in interference control

Authors: Krawczyk D.C., Morrison R.G., Viskontas I., Holyoak K.J., Chow T.W., Mendez M.F., Miller B.L., Knowlton B.J.
Publication Date: February, 2008

We compared the reasoning performance of patients with frontal-variant frontotemporal lobar degeneration (FTLD) with that of patients with temporal-variant FTLD and healthy controls. In a picture analogy task with a multiple-choice answer format, frontal-variant FTLD patients performed less accurately than temporal-variant FTLD patients, who in turn performed worse than healthy controls, when semantic and perceptual distractors were present among the answer choices. When the distractor answer choices were eliminated, frontal-variant patients showed relatively greater improvement in performance. Similar patient groups were tested with a relational-pattern reasoning task that included manipulations of one or two relations and both perceptual and semantic extraneous information. Frontal-variant patients showed performance deficits on all tasks relative to the other subject groups, especially when distracted. These results demonstrate that intact prefrontal cortex (PFC) is necessary for controlling interference from perceptual and semantic distractors in order to reason from relational structure.

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Differences in task demands influence the hemispheric lateralization and neural correlates of metaphor

Authors: Yang F.G., Edens J., Simpson C., Krawczyk D.C.
Publication Date: September, 2009

This study investigated metaphor comprehension in the broader context of task-difference effects and manipulation of processing difficulty. We predicted that right hemisphere recruitment would show greater specificity to processing difficulty rather than metaphor comprehension. Previous metaphor processing studies have established that the left inferior frontal gyrus strongly correlates with metaphor comprehension but there has been controversy about whether right hemisphere (RH) involvement is specific for metaphor comprehension. Functional MRI data were recorded from healthy subjects who read novel metaphors, conventional metaphors, definition-like sentences, or literal sentences. We investigated metaphor processing in contexts where semantic judgment or imagery modulates linguistic judgment. Our findings support the position that the type of task rather than figurative language processing per se modulates the left inferior gyrus (LIFG). RH involvement was more influenced by processing difficulty and less by the novelty or figurativity of linguistic expressions. Our results suggest that figurative language processing depends upon the effects of task-type and processing difficulty on imaging results.

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Figurative language processing after traumatic brain injury in adults: A preliminary study

Authors: Yang F.G., Fuller J., Khodaparast N., Krawczyk D.C.
Publication Date: March, 2010

Figurative speech (e.g., proverb, irony, metaphor, and idiom) has been reported to be particularly sensitive to measurement of abstract thinking in patients who suffer from impaired abstraction and language abilities. Metaphor processing was investigated with fMRI in adults with moderate to severe postacute traumatic brain injury (TBI) and healthy age-matched controls using a valence-judgment task. We hypothesized that TBI patients would display decreased activation of the left inferior frontal gyrus (LIFG), which is considered central to semantic memory retrieval and abstract thought, in comparison with healthy controls.Wealso predicted that decreased activation in TBI individuals would correlate with their behavioral response times. A whole-brain analysis across the two participant groups revealed that patients did not strongly engage frontal and temporal regions related to semantic processing for novel metaphor comprehension, whereas control participants exhibited more intensive and concentrated activation within frontal and temporal areas. A region of interest (ROI) analysis verified that the LIFG was underactivated in TBI patients compared to controls across all conditions. TBI patients’ impaired abstraction of novel stimuli may stem from reduced prefrontal control of semantic memory as well as disrupted interconnectivity of prefrontal cortex with other regions.

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An fMRI investigation of cognitive stages in reasoning by analogy

Authors: Krawczyk D.C., McClelland M.M., Donovan C.M., Tillman G.D., Maguire M.J.
Publication Date: April, 2010

We compared reasoning about four-termanalogy problems in the format (A:B::C: D) to semantic and perceptual control conditions that required matching without analogical mapping. We investigated distinct phases of the problem solving process divided into encoding, mapping/ inference, and response. Using fMRI, we assessed the brain activation relevant to each of these phaseswithanemphasis onachieving a betterunderstandingof analogical reasoningrelative to these other matching conditions. We predicted that the analogical condition would involve the most cognitive effort in the encoding and mapping/inference phases, while the control conditions were expected to engage greater prefrontal cortex (PFC) activation at the response period. Results showed greater activation for the analogical condition relative to the control conditions at the encoding phase in several predominantly left lateralized and medial areas of the PFC. Similar resultswere observed for themapping/inference phase, though this difference was limited to the left PFC and rostral PFC. The response phase resulted in the fastest and most accurate responses in the analogy condition relative to the control conditions. This was accompanied by greater processing within the left lateral and the medial PFC for the control conditions relative to the analogy condition, consistent with most of the cognitive processing of the analogy condition having occurred in the prior task phases.Overallwe demonstrate that the left ventral and dorsal lateral, medial, and rostral PFC are important in both the encoding of relational information, mapping and inference processes, and verification of semantic and perceptual responses in four term analogical reasoning.

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Deficits in analogical reasoning in adolescents with traumatic brain injury

Authors: Krawczyk D.C., Hanten G., Wilde E.A., Li X., Schnelle K.P., Merkley T.L., Vasquez A.C., Cook L.G., McClelland M., Chapman S.B., Levin H.S.
Publication Date: August, 2010

Individuals with traumatic brain injury (TBI) exhibit deficits in executive control, which may impact their reasoning abilities. Analogical reasoning requires working memory and inhibitory abilities. In this study, we tested adolescents with moderate to severe TBI and typically developing (TD) controls on a set of picture analogy problems. Three factors were varied: complexity (number of relations in the problems), distraction (distractor item present or absent), and animacy (living or non-living items in the problems). We found that TD adolescents performed significantly better overall than TBI adolescents. There was also an age effect present in the TBI group where older participants performed better than younger ones. This age effect was not observed in the TD group. Performance was affected by complexity and distraction. Further, TBI participants exhibited lower performance with distractors present than TD participants. The reasoning deficits exhibited by the TBI participants were correlated with measures of executive function that required working memory updating, attention, and attentional screening. Using MRI-derived measures of cortical thickness, correlations were carried out between task accuracy and cortical thickness. The TD adolescents showed negative correlations between thickness and task accuracy in frontal and temporal regions consistent with cortical maturation in these regions. This study demonstrates that adolescent TBI results in impairments in analogical reasoning ability. Further, TBI youth have difficulty effectively screening out distraction, which may lead to failures in comprehension of the relations among items in visual scenes. Lastly, TBI youth fail to show robust cortical–behavior correlations as observed in TD individuals.

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A hierarchy for relational reasoning in the prefrontal cortex

Authors: Krawczyk D.C., Michelle McClelland M., Donovan C.M.
Publication Date: May, 2010

The human brain possesses a unique capacity to reason about abstract relationships among items in our environment. The neural organization of reasoning abilities has remained elusive. Two approaches toward investigating human reasoning have involved studying visuo-spatial reasoning abilities and studying analogical reasoning. These approaches have both revealed anterior prefrontal cortex (PFC) involvement, but no prior studies have jointly investigated these two forms of reasoning to understand any potential convergence of activation within the PFC. Using fMRI, we tested the extent to which these two forms of reasoning (visuo-spatial and analogical) overlap in PFC activation. We conducted a visuo-spatial reasoning task that required processing multiple changes across three abstract pictures. This task activated a progressively anterior series of PFC regions when multiple relations had to be integrated. We also conducted a four-term analogy task in a stage-wise manner and compared results from this task to semantic and perceptual control conditions that did not require integrating relations across the problems. We found greater activation for analogical reasoning in the series of PFC regions that were sequentially involved in the visuo-spatial reasoning task. These findings indicate that stages of neural processing overlap for different domains within human reasoning. The pattern of differences across the analogy task suggests a hierarchical organization for relational reasoning across domains in which posterior frontal cortex is active across concrete reasoning tasks, while progressively more anterior regions are recruited to process increasingly abstract representations in reasoning.

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The neural organization of perception in chess experts

Authors: Krawczyk D.C., Boggan A.L., McClelland M.M., Bartlett J.C.
Publication Date: May, 2011

The human visual system responds to expertise, and it has been suggested that regions that process faces also process other objects of expertise including chess boards by experts. We tested whether chess and face processing overlap in brain activity using fMRI. Chess experts and novices exhibited face selective areas, but these regions showed no selectivity to chess configurations relative to other stimuli. We next compared neural responses to chess and to scrambled chess displays to isolate areas relevant to expertise. Areas within the posterior cingulate, orbitofrontal cortex, and right temporal cortex were active in this comparison in experts over novices. We also compared chess and face responses within the posterior cingulate and found this area responsive to chess only in experts. These findings indicate that the configurations in chess are not strongly processed by face-selective regions that are selective for faces in individuals who have expertise in both domains. Further, the area most consistently involved in chess did not show overlap with faces. Overall, these results suggest that expert visual processing may be similar at the level of recognition, but need not show the same neural correlates.

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Brain activation during a social attribution task in adolescents with moderate to severe traumatic brain injury

Authors: Scheibel R.S., Newsome M.R., Wilde E.A., McClelland M.M., Hanten G., Krawczyk D.C., Cook L.G., Chu Z.D., Vasquez A.C., Yallampalli R., Lin X., Hunter J.V., Levin H.S.
Publication Date: July, 2011

The ability to make accurate judgments about the mental states of others, sometimes referred to as theory of mind (ToM), is often impaired following traumatic brain injury (TBI), and this deficit may contribute to problems with interpersonal relationships. The present study used an animated social attribution task (SAT) with functional magnetic resonance imaging (fMRI) to examine structures mediating ToM in adolescents with moderate to severe TBI. The study design also included a comparison group of matched, typically developing (TD) adolescents. The TD group exhibited activation within a number of areas that are thought to be relevant to ToM, including the medial prefrontal and anterior cingulate cortex, fusiform gyrus, and posterior temporal and parietal areas. The TBI subjects had significant activation within many of these same areas, but their activation was generally more intense and excluded the medial prefrontal cortex. Exploratory regression analyses indicated a negative relation between ToM-related activation and measures of white matter integrity derived from diffusion tensor imaging, while there was also a positive relation between activation and lesion volume. These findings are consistent with alterations in the level and pattern of brain activation that may be due to the combined influence of diffuse axonal injury and focal lesions.

PubMed ID: 21777109
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Impaired neural processing of social attribution in anorexia nervosa

Authors: McAdams C.J., Krawczyk D.C.
Publication Date: June, 2011

Anorexia nervosa (AN) patients have been found to have problems in social cognition, including the process of thinking about other people's thoughts and feelings, often referred to as Theory of Mind (ToM). We examined neural correlates relating to thinking about social relationships in 17 women in recovery from anorexia (RAN) and 17 healthy women (CON) using a functional magnetic resonance imaging (fMRI) task. The task consisted of short videos of moving shapes that subjects viewed either in the context of performing a social decision related to how the shapes interacted: “People: All friends?” or in the context of performing a visuospatial task related to how the shapes moved after bumping into each other: “Bumper cars: Same weight?”. The RAN participants showed reduced activation in the social cognition network, with the most robust differences in the right temporoparietal junction (RTPJ). There were no significant differences between the CON and RAN groups in regions more active during the visuospatial task. These neural correlates show differences in the processing of social knowledge in RAN subjects suggesting that biological impairments in social cognition may contribute to pathology in AN.

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Modulation of working memory function by motivation through loss-aversion

Authors: Krawczyk D.C., D'Esposito M.
Publication Date: August, 2011

Abstract: Cognitive performance is affected by motivation. Few studies, however, have investigated the neural mechanisms of the influence of motivation through potential monetary punishment on working memory. We employed functional MRI during a delayed recognition task that manipulated top-down control demands with added monetary incentives to some trials in the form of potential losses of bonus money. Behavioral performance on the task was influenced by loss-threatening incentives in the form of faster and more accurate performance. As shown previously, we found enhancement of activity for relevant stimuli occurs throughout all task periods (e.g., stimulus encoding, maintenance, and response) in both prefrontal and visual association cortex. Further, these activation patterns were enhanced for trials with possible monetary loss relative to nonincentive trials. During the incentive cue, the amygdala and striatum showed significantly greater activation when money was at a possible loss on the trial. We also evaluated patterns of functional connectivity between regions responsive to monetary consequences and prefrontal areas responsive to the task. This analysis revealed greater delay period connectivity between and the left insula and prefrontal cortex with possible monetary loss relative to nonincentive trials. Overall, these results reveal that incentive motivation can modulate performance on working memory tasks through top-down signals via amplification of activity within prefrontal and visual association regions selective to processing the perceptual inputs of the stimuli to be remembered.

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Brief Report: Insight into Illness and Social Attributional Style in Asperger's Syndrome

Authors: Didehbani N., Shad M.U., Kandalaft M.R., Allen T.T., Tamminga C.A., Krawczyk D.C., Chapman S.B.
Publication Date: April, 2012

Abstract A number of psychiatric illnesses have been recognized to have some level of insight deficits, including developmental disorders, such as Asperger’s Syndrome (ASP). However insight into illness has not been empirically investigated in ASP and little research has examined how individuals with ASP view their deficits. This is the first study to assess insight and the relationship between insight and externalizing bias (EB) in ASP. Participants with ASP (n = 21) and healthy controls (n = 24) were recruited. Attributional style was assessed with the internal, personal, and situational attribution questionnaire. Insight was assessed with both a clinician-administered and a selfadministered measure. Results revealed that EB was negatively correlated with insight as assessed with the clinician- administered but not the self-administered measure of insight.

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The network architecture of cortical processing in visuo-spatial reasoning

Authors: Ehsan S.-K., Motes M.A., Rypma B., Krawczyk D.C.
Publication Date: May, 2012

Reasoning processes have been closely associated with prefrontal cortex (PFC), but specifically emerge from interactions among networks of brain regions. Yet it remains a challenge to integrate these brain-wide interactions in identifying the flow of processing emerging from sensory brain regions to abstract processing regions, particularly within PFC. Functional magnetic resonance imaging data were collected while participants performed a visuo-spatial reasoning task. We found increasing involvement of occipital and parietal regions together with caudal-rostral recruitment of PFC as stimulus dimensions increased. Brain-wide connectivity analysis revealed that interactions between primary visual and parietal regions predominantly influenced activity in frontal lobes. Caudal-to-rostral influences were found within left-PFC. Right-PFC showed evidence of rostral-to-caudal connectivity in addition to relatively independent influences from occipito-parietal cortices. In the context of hierarchical views of PFC organization, our results suggest that a caudal-to-rostral flow of processing may emerge within PFC in reasoning tasks with minimal top-down deductive requirements.

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Insight and empathy in schizophrenia

Authors: Didehbani N., Shad M.U., Tamminga C.A., Kandalaft M.R., Allen T.T., Chapman S.B., Krawczyk D.C.
Publication Date: July, 2012

Letter to the Editors

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Virtual reality social cognition training for young adults with high-functioning autism

Authors: Kandalaft M.R., Didehbani N., Krawczyk D.C., Allen T.T., Chapman S.B.
Publication Date: May, 2012

Abstract Few evidence-based social interventions exist for young adults with high-functioning autism, many of whom encounter significant challenges during the transition into adulthood. The current study investigated the feasibility of an engaging Virtual Reality Social Cognition Training intervention focused on enhancing social skills, social cognition, and social functioning. Eight young adults diagnosed with high-functioning autism completed 10 sessions across 5 weeks. Significant increases on social cognitive measures of theory of mind and emotion recognition, as well as in real life social and occupational functioning were found post-training. These findings suggest that the virtual reality platform is a promising tool for improving social skills, cognition, and functioning in autism.

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Deficits in functional connectivity of hippocampal and frontal lobe circuits after traumatic axonal injury

Authors: Marquez De La Plata C.D., Garces J., Kojori E.S., Grinnan J., Krishnan K., Pidikiti R., Spence J., Devous Sr. M.D., Moore C., McColl R., Madden C., Diaz-Arrastia R.
Publication Date: January, 2011

Objective: To examine the functional connectivity of hippocampal and selected frontal lobe circuits in patients with traumatic axonal injury (TAI). Design: Observational study. Setting: An inpatient traumatic brain injury unit. Imaging and neurocognitive assessments were conducted in an outpatient research facility. Participants: Twenty-five consecutive patients with brain injuries consistent with TAI and acute subcortical white matter abnormalities were studied as well as 16 healthy volunteers of similar age and sex. Interventions: Echo-planar and high-resolution T1- weighted images were acquired using 3-T scanners. Regions of interest (ROI) were drawn bilaterally for the hippocampus, anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex and were used to extract time series data. Blood oxygenation level–dependent data from each ROI were used as reference functions for correlating with all other brain voxels. Interhemispheric functional connectivity was assessed for each participant by correlating homologous regions using a Pearson correlation coefficient. Patient functional and neurocognitive outcomes were assessed approximately 6 months after injury. Main Outcome Measures: Interhemispheric functional connectivity, spatial patterns of functional connectivity, and associations of connectivity measures with functional and neurocognitive outcomes. Results: Patients showed significantly lower interhemispheric functional connectivity for the hippocampus and ACC. Controls demonstrated stronger and more focused functional connectivity for the hippocampi and ACC, and a more focused recruitment of the default mode network for the dorsolateral prefrontal cortex ROI. The interhemispheric functional connectivity for the hippocampus was correlated with delayed recall of verbal information. Conclusions: Traumatic axonal injury may affect interhemispheric neural activity, as patients with TAI show disrupted interhemispheric functional connectivity. More careful investigation of interhemispheric connectivity is warranted, as it demonstrated a modest association with outcome in chronic TBI.

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Magnetic resonance imaging of diffuse axonal injury: Quantitative assessment of white matter lesion volume

Authors: Marquez De La Plata C., Ardelean A., Koovakkattu D., Srinivasan P., Miller A., Phuong V., Harper C., Moore C., Whittemore A., Madden C., Diaz-Arrastia R., Devous Sr. M.
Publication Date: April, 2007

Diffuse axonal injury (DAI) is a common mechanism of traumatic brain injury (TBI) for which there is no well-accepted anatomic measures of injury severity. The present study aims to quantitatively assess DAI by measuring white matter lesion volume visible in fluid-attenuated inversion recovery (FLAIR) weighted images and to determine whether higher lesion volumes are associated with unfavorable functional outcome 6 months after injury. Twenty-four patients who experienced moderate to severe TBI without extra-axial or major cortical contusions were included in this study. Lesion volume was assessed by quantifying areas of hyperintensities in the white matter utilizing digitized FLAIR images. Two independent raters processed the magnetic resonance (MR) images and determined the total DAI volume. Functional outcome was assessed at 6 months after injury using the Glasgow Outcome Scale–Extended (GOSE). Interclass correlation analyses showed very high interrater reliability for each measure between the two raters (Interclass Correlation Coefficient = 0.95, p ≤ 0.001). Total DAI volume was significantly, although modestly, correlated to GOSE (r = −0.453, p = 0.034). White matter lesion volume resulting from DAI can be quantitatively and reliably assessed from standard FLAIR-weighted MRIs. Patients with greater DAI volume have poorer functional outcomes. These methods may be useful in stratifying injury severity and for the assessment of DAI-directed therapies.

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Racial Differences in Employment Outcomes After Traumatic Brain Injury

Authors: Arango-Lasprilla J.C., Ketchum J.M., Williams K., Kreutzer J.S., Marquez de la Plata C.D., O'Neil-Pirozzi T.M., Wehman P.
Publication Date: May, 2008

Abstract Arango-Lasprilla JC, Ketchum JM, Williams K, Kreutzer JS, Marquez de la Plata CD, O'Neil-Pirozzi TM, Wehman P. Racial differences in employment outcomes after traumatic brain injury. Objective To examine racial differences in employment status and occupational status 1 year after a traumatic brain injury (TBI). Design Retrospective study. Setting Longitudinal dataset of the Traumatic Brain Injury Model Systems national database. Participants Subjects with primarily moderate to severe TBI (3468 whites vs 1791 minorities) hospitalized between 1989 and 2005. Interventions Not applicable. Main Outcome Measures Employment status (competitively employed or unemployed) and occupational status (professional/managerial, skilled, or manual labor) at 1 year postinjury. Results Race and/or ethnicity has a significant effect on employment status at 1 year postinjury (View the MathML sourceχ12=58.23, P<.001), after adjusting for preinjury employment status, sex, Disability Rating Scale at discharge, marital status, cause of injury, age, and education. The adjusted odds of being unemployed versus competitively employed are 2.17 times (95% confidence interval, 1.78–2.65) greater for minorities than for whites. Race and ethnicity does not have a significant effect on occupational status at 1 year postinjury. Conclusions With this empirical evidence supporting racial differences in employment outcomes between minorities and whites at 1 year postinjury, priority should be given to tailoring interventions to maximize minority survivors' work-related productivity.

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Diffusion tensor tractography of traumatic diffuse axonal injury

Authors: Wang J.Y., Bakhadirov K., Devous Sr. M.D., Abdi H., McColl R., Moore C., Marquez De La Plata C.D., Ding K., Whittemore A., Babcock E., Rickbeil T., Dobervich J., Kroll D., Dao B., Mohindra N., Madden C.J., Diaz-Arrastia R.
Publication Date: May, 2008

Background Diffuse axonal injury is a common consequence of traumatic brain injury that frequently involves the parasagittal white matter, corpus callosum, and brainstem. Objective To examine the potential of diffusion tensor tractography in detecting diffuse axonal injury at the acute stage of injury and predicting long-term functional outcome. Design Tract-derived fiber variables were analyzed to distinguish patients from control subjects and to determine their relationship to outcome. Setting Inpatient traumatic brain injury unit. Patients From 2005 to 2006, magnetic resonance images were acquired in 12 patients approximately 7 days after injury and in 12 age- and sex-matched controls. Main Outcome Measures Six fiber variables of the corpus callosum, fornix, and peduncular projections were obtained. Glasgow Outcome Scale–Extended scores were assessed approximately 9 months after injury in 11 of the 12 patients. Results At least 1 fiber variable of each region showed diffuse axonal injury–associated alterations. At least 1 fiber variable of the anterior body and splenium of the corpus callosum correlated significantly with the Glasgow Outcome Scale–Extended scores. The predicted outcome scores correlated significantly with actual scores in a mixed-effects model. Conclusion Diffusion tensor tractography–based quantitative analysis at the acute stage of injury has the potential to serve as a valuable biomarker of diffuse axonal injury and predict long-term outcome.

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Impact of Age on Long-Term Recovery From Traumatic Brain Injury

Authors: Marquez de la Plata C.D., Hart T., Hammond F.M., Frol A.B., Hudak A., Harper C.R., O'Neil-Pirozzi T.M., Whyte J., Carlile M., Diaz-Arrastia R.
Publication Date: May, 2008

Objective: To determine whether older persons are at increased risk for progressive functional decline after traumatic brain injury (TBI). Design: Longitudinal cohort study. Setting: Traumatic Brain Injury Model Systems (TBIMS) rehabilitation centers. Participants: Subjects enrolled in the TBIMS national dataset. Interventions: Not applicable. Main Outcome Measures: Disability Rating Scale (DRS), FIM instrument cognitive items, and the Glasgow Outcome Scale–Extended. Results: Participants were separated into 3 age tertiles: youngest (16–26y), intermediate (27–39y), and oldest (40y). DRS scores were comparable across age groups at admission to a rehabilitation center. The oldest group was slightly more disabled at discharge from rehabilitation despite having less severe acute injury severity than the younger groups. Although DRS scores for the 2 younger groups improved significantly from year 1 to year 5, the greatest magnitude of improvement in disability was seen among the youngest group. In addition, after dividing patients into groups according to whether their DRS scores improved (13%), declined (10%), or remained stable (77%) over time, the likelihood of decline was found to be greater for the 2 older groups than for the youngest group. A multiple regression model showed that age has a significant negative influence on DRS score 5 years post-TBI after accounting for the effects of covariates. Conclusions: This study supported our primary hypothesis that older patients show greater decline over the first 5 years after TBI than younger patients. In addition, the greatest amount of improvement in disability was observed among the youngest group of survivors. These results suggest that TBI survivors, especially older patients, may be candidates for neuroprotective therapies after TBI.

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The Influence of Minority Status on Job Stability After Traumatic Brain Injury

Authors: Arango-Lasprilla J.C., Ketchum J.M., Gary K.W., Kreutzer J.S., O'Neil-Pirozzi T.M., Wehman P., Marquez de la Plata C., Jha A.
Publication Date: January, 2009

Objective: To determine the influence of minority status on job stability after traumatic brain injury (TBI). Setting: TBI Model Systems Centers. Participants: 633 individuals (414 Caucasians vs. 219 Minorities) with primarily moderate to severe TBI hospitalized at one of the TBI Model Systems Centers between 1988 and 2001 with 3 years of continuous follow up employment data after discharge. Main Outcome Measures: Job stability was defined as “stable” (competitively employed at all three follow-up visits), “unemployed” (not competitively employed at all three visits), and “unstable” (any other mixture of competitively employed and not competitively employed over the three follow-up visits). Methods: A multinomial logistic regression model was used to model the effect of ethnicity on job stability post TBI after adjusting for injury and demographic characteristics. Results: Compared to Caucasians, the adjusted odds for minorities were 3.587 times greater for being unemployed versus being stably employed (95% CI 1.930, 6.668), 1.911 times greater for being unstably employed versus being stably employed (95% CI 1.006, 3.628), and 1.878 times more greater for being unemployed versus being unstably employed (95% CI 1.157, 3.046) after adjusting for preinjury employment status, age, marital status, education, cause of injury, total length of stay in acute and rehabilitation hospitals, and DRS at discharge. Conclusions: Minority status is an independent predictor of short-term job stability after TBI. Minority TBI survivors were more likely than Caucasians to be unemployed or unstably employed. Rehabilitation professionals should develop employment interventions that will address the specific needs of these racial/ethnic groups and facilitate optimal employment outcomes for minority TBI survivors.

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Regionally selective atrophy after traumatic axonal injury

Authors: Warner M.A., Youn T.S., Davis T., Chandra A., Marquez De La Plata C., Moore C., Harper C., Madden C.J., Spence J., McColl R., Devous M., King R.D., Diaz-Arrastia R.
Publication Date: July, 2010

Objectives: To determine the spatial distribution of cortical and subcortical volume loss in patients with diffuse traumatic axonal injury and to assess the relationship between regional atrophy and functional outcome. Design: Prospective imaging study. Longitudinal changes in global and regional brain volumes were assessed using high-resolution magnetic resonance imaging–based morphometric analysis. Setting: Inpatient traumatic brain injury unit. Patients or Other Participants: Twenty-five patients with diffuse traumatic axonal injury and 22 ageand sex-matched controls. Main Outcome Measure: Changes in global and regional brain volumes between initial and follow-up magnetic resonance imaging were used to assess the spatial distribution of posttraumatic volume loss. The Glasgow Outcome Scale–Extended score was the primary measure of functional outcome. Results: Patients underwent substantial global atrophy with mean whole-brain parenchymal volume loss of 4.5% (95% confidence interval, 2.7%-6.3%). Decreases in volume (at a false discovery rate of 0.05) were seen in several brain regions including the amygdala, hippocampus, thalamus, corpus callosum, putamen, precuneus, postcentral gyrus, paracentral lobule, and parietal and frontal cortices, while other regions such as the caudate and inferior temporal cortex were relatively resistant to atrophy. Loss of whole-brain parenchymal volume was predictive of long-term disability, as was atrophy of particular brain regions including the inferior parietal cortex, pars orbitalis, pericalcarine cortex, and supramarginal gyrus. Conclusion: Traumatic axonal injury leads to substantial posttraumatic atrophy that is regionally selective rather than diffuse, and volume loss in certain regions may have prognostic value for functional recovery.

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Diffusion tensor imaging biomarkers for traumatic axonal injury: Analysis of three analytic methods

Authors: Marquez De La Plata C.D., Yang F.G., Wang J.Y., Krishnan K., Bakhadirov K., Paliotta C., Aslan S., Devous M.D., Moore C., Harper C., McColl R., Munro Cullum C., Diaz-Arrastia R.
Publication Date: March, 2010

Traumatic axonal injury (TAI) is a common mechanism of traumatic brain injury not readily identified using conventional neuroimaging modalities. Novel imaging modalities such as diffusion tensor imaging (DTI) can detect microstructural compromise in white matter (WM) in various clinical populations including TAI. DTI-derived data can be analyzed using global methods (i.e., WM histogram or voxel-based approaches) or a regional approach (i.e., tractography). While each of these methods produce qualitatively comparable results, it is not clear which is most useful in clinical research and ultimately in clinical practice. This study compared three methods of analyzing DTI-derived data with regard to detection of WM injury and their association with clinical outcomes. Thirty patients with TAI and 19 demographically similar normal controls were scanned using a 3 Tesla magnet. Patients were scanned approximately eight months postinjury, and underwent an outcomes assessment at that time. Histogram analysis of fractional anisotropy (FA) and mean diffusivity showed global WM integrity differences between patients and controls. Voxel-based and tractography analyses showed significant decreases in FA within centroaxial structures involved in TAI. All three techniques were associated with functional and cognitive outcomes. DTI measures of microstructural integrity appear robust, as the three analysis techniques studied showed adequate utility for detecting WM injury.

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Brain morphometry changes and depressive symptoms after traumatic brain injury

Authors: Hudak A., Warner M., Marquez de la Plata C., Moore C., Harper C., Diaz-Arrastia R.
Publication Date: October, 2010

Traumatic brain injury (TBI) is associated with an increased risk of depressive symptoms. Recent imaging studies on spontaneous depression have implicated several brain structures; however, few studies have done the same for post-TBI depression. We report on a pilot observational study correlating atrophy of brain regions of interest in subjects after TBI with depressive symptoms measured by the Beck Depression Inventory-II. Regional brain volumes were calculated on both acute and 6-month MRI using an automated segmentation algorithm (FreeSurfer). Percent volume changes in brain regions were correlated with BDI-II scores using Spearman's rank order correlation coefficient. Correction for multiple comparisons was performed using the false discovery rate (FDR). Three regions of interest (left rostral anterior cingulate and bilateral orbitofrontal cortex) were found to be significantly correlated with depressive symptoms (FDR 0.05). With FDR 0.1, six regions were significantly correlated. The use of volumetric analysis of brain regions of interest to study post-TBI depression is worthy of further study. Regions associated with depressive symptoms in this pilot study were similar to those implicated in study of spontaneous depression.

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Longitudinal changes of structural connectivity in traumatic axonal injury

Authors: Wang J.Y., Bakhadirov K., Abdi H., Devous M.D., Marquez De La Plata C.D., Moore C., Madden C.J., Diaz-Arrastia R.
Publication Date: August, 2011

Objectives: To identify structural connectivity change occurring during the first 6 months after traumatic brain injury and to evaluate the utility of diffusion tensor tractography for predicting long-term outcome. Methods: The participants were 28 patients with mild to severe traumatic axonal injury and 20 age- and sex-matched healthy control subjects. Neuroimaging was obtained 0–9 days postinjury for acute scans and 6–14 months postinjury for chronic scans. Long-term outcome was evaluated on the day of the chronic scan. Twenty-eight fiber regions of 9 major white matter structures were reconstructed, and reliable tractography measurements were determined and used. Results: Although most (23 of 28) patients had severe brain injury, their long-term outcome ranged from good recovery (16 patients) to moderately (5 patients) and severely disabled (7 patients). In concordance with the diverse outcome, the white matter change in patients was heterogeneous, ranging from improved structural connectivity, through no change, to deteriorated connectivity. At the group level, all 9 fiber tracts deteriorated significantly with 7 (corpus callosum, cingulum, angular bundle, cerebral peduncular fibers, uncinate fasciculus, and inferior longitudinal and fronto-occipital fasciculi) showing structural damage acutely and 2 (fornix body and left arcuate fasciculus) chronically. Importantly, the amount of change in tractography measurements correlated with patients’ long-term outcome. Acute tractography measurements were able to predict patients’ learning and memory performance; chronic measurements also determined performance on processing speed and executive function. Conclusions: Diffusion tensor tractography is a valuable tool for identifying structural connectivity changes occurring between the acute and chronic stages of traumatic brain injury and for predicting patients’ long-term outcome.

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Virtual Reality Social Cognition Training for Young Adults with High-Functioning Autism

Authors: Michelle R. Kandalaft; Nyaz Didehbani; Daniel C. Krawczyk; Tandra T. Allen; Sandra B. Chapman
Publication Date: May, 2012

Few evidence-based social interventions exist for young adults with high-functioning autism, many of whom encounter significant challenges during the transition into adulthood. The current study investigated the feasibility of an engaging Virtual Reality Social Cognition Training intervention focused on enhancing social skills, social cognition, and social functioning. Eight young adults diagnosed with high-functioning autism completed 10 sessions across 5 weeks. Significant increases on social cognitive measures of theory of mind and emotion recognition, as well as in real life social and occupational functioning were found post-training. These findings suggest that the virtual reality platform is a promising tool for improving social skills, cognition, and functioning in autism.

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The Wechsler ACS Social Perception Subtest: A Preliminary Comparison With Other Measures of Social Cognition

Authors: Michelle R. Kandalaft; Nyaz Didehbani; C. Munro Cullum; Daniel C. Krawczyk; Tandra T. Allen; Carol A. Tamminga; Sandra B. Chapman
Publication Date: April, 2012

Relative to other cognitive areas, there are few clinical measures currently available to assess social perception. A new standardized measure, the Wechsler Advanced Clinical Solutions (ACS) Social Perception subtest, addresses some limitations of existing measures; however, little is known about this new test. The first goal of this investigation was to preliminarily explore the relationship of the ACS Social Perception subtest to five other measures of social perception and cognition in a sample of control subjects and individuals with Asperger Syndrome and schizophrenia. A secondary goal was to preliminarily explore the differences between groups on six measures of social perception and cognition. Results revealed several significant correlations between the ACS Social Perception subtest and other measures of social cognition, and some evidence for the distinguishing abilities of the measure. The ACS Social Perception subtest appears to be a promising measure for the evaluation of social perceptive skills.

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Recommendations for the Use of Common Outcome Measures in Pediatric Traumatic Brain Injury Research

Authors: Stephen R. McCauley; Elisabeth A. Wilde; Vicki A. Anderson; Gary Bedell; Sue R. Beers; Thomas F. Campbell; Sandra B. Chapman; Linda Ewing-Cobbs; Joan P. Gerring; Gerard A. Gioia; Harvey S. Levin; Linda J. Michaud; Mary R. Prasad; Bonnie R. Swaine; Lyn S. Turkstra; Shari L. Wade; Keith O. Yeates
Publication Date: March, 2012

This article addresses the need for age-relevant outcome measures for traumatic brain injury (TBI) research and summarizes the recommendations by the inter-agency Pediatric TBI Outcomes Workgroup. The Pediatric Workgroup’s recommendations address primary clinical research objectives including characterizing course of recovery from TBI, prediction of later outcome, measurement of treatment effects, and comparison of outcomes across studies. Consistent with other Common Data Elements (CDE) Workgroups, the Pediatric TBI Outcomes Workgroup adopted the standard three-tier system in its selection of measures. In the first tier, core measures included valid, robust, and widely applicable outcome measures with proven utility in pediatric TBI from each identified domain including academics, adaptive and daily living skills, family and environment, global outcome, health-related quality of life, infant and toddler measures, language and communication, neuropsychological impairment, physical functioning, psychiatric and psychological functioning, recovery of consciousness, social role participation and social competence, social cognition, and TBI-related symptoms. In the second tier, supplemental measures were recommended for consideration in TBI research focusing on specific topics or populations. In the third tier, emerging measures included important instruments currently under development, in the process of validation, or nearing the point of published findings that have significant potential to be superior to measures in the core and supplemental lists and may eventually replace them as evidence for their utility emerges.

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Reward circuit function in high BMI individuals with compulsive overeating: Similarities with addiction

Authors: Francesca M. Filbey; Ursula S. Myers; Samuel DeWitt
Publication Date: August, 2012

Context: The rising rate of overweight and obese individuals among developing countries despite focused efforts on prevention and treatment underscores not only the need to better define the physiological factors that contribute to weight problems, but also the need to elucidate the neurobiological mechanisms of the self-regulatory failure over eating that leads to weight problems. Emergent findings suggest an overlapping model of addiction and compulsive overeating. Objective: Our goal was to examine whether neural hyper-responsivity to reward typically associated with substance abuse could also be seen in individuals exhibiting binge-eating behavior. Design: Participants completed self-assessments of demographic information and eating behavior. Neurofunctional data were collected via functional MRI (fMRI) scans while participants were exposed to personally relevant highcalorie cues. Setting: The participants were recruited from the general community. Participants: Twenty‐six individuals with high body mass index (BMI)>25 and moderate binge‐eating behavior as assessed by the Binge Eating Scale (BES) were recruited for this study. Main Outcome Measures: fMRI BOLD response during exposure to high-calorie taste cues. Results: The results showed that exposure to high-calorie taste cues elicited fMRI BOLD response in the reward system of individuals with high BMI, and, more importantly, that this hyper-responsivity increases with greater number of binge‐eating symptoms (cluster-corrected pb.05, z=1.9). Conclusions: These findings support an overlapping neural model of addiction and self-regulatory failure over eating that may lead to problems with weight in humans. These findings offer insight into the prevention and treatment of disordered eating.

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Cannabis cue-elicited craving and the reward neurocircuitry

Authors: Francesca M. Filbey; Samuel J. DeWitt
Publication Date: November, 2012

Cue-elicited craving or the intense desire to consume a substance following exposure to a conditioned drug cue is one of the primary behavioral symptoms of substance use disorders (SUDs). While the concept of cueelicited craving is well characterized in alcohol and other substances of abuse, only recently has it been described in cannabis. A review of the extant literature has established that cue-elicited craving is a powerful reinforcer that contributes to drug-seeking for cannabis. Further, emergent research has begun to identify the neurobiological systems and neural mechanisms associated with this behavior. What research shows is that while theories of THC's effects on the dopaminergic-reward system remain divergent, cannabis cues elicit neural activation in the brain's reward network.

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Associations between Cannabinoid Receptor-1 (CNR1) Variation and Hippocampus and Amygdala Volumes in Heavy Cannabis Users

Authors: Joseph P Schacht; Kent E Hutchison; Francesca M Filbey
Publication Date: June, 2012

Heavy cannabis users display smaller amygdalae and hippocampi than controls, and genetic variation accounts for a large proportion of variance in liability to cannabis dependence (CD). A single nucleotide polymorphism in the cannabis receptor-1 gene (CNR1), rs2023239, has been associated with CD diagnosis and intermediate phenotypes, including abstinence-induced withdrawal, cue-elicited craving, and parahippocampal activation to cannabis cues. This study compared hippocampal and amygdalar volumes (potential CD intermediate phenotypes) between heavy cannabis users and healthy controls, and analyzed interactions between group, rs2023239 variation, and the volumes of these structures. Ninety-four heavy cannabis users participated, of whom 37 (14 men, 23 women; mean age¼27.8) were matched to 37 healthy controls (14 men, 23 women; mean age¼27.3) for case-control analyses. Controlling for total intracranial volume and other confounding variables, matched cannabis users had smaller bilateral hippocampi (left, p¼0.002; right, p¼0.001) and left amygdalae (p¼0.01) than controls. When genotype was considered in the case-control analyses, there was a group by genotype interaction, such that the rs2023239 G allele predicted lower volume of bilateral hippocampi among cannabis users relative to controls (both po0.001). This interaction persisted when all 94 cannabis users were compared to controls. There were no group by genotype interactions on amygdalar volume. These data replicate previous findings of reduced hippocampal and amygdalar volume among heavy cannabis users, and suggest that CNR1 rs2023239 variation may predispose smaller hippocampal volume after heavy cannabis use. This association should be tested in future studies of brain volume differences in CD.

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Visual event-related potentials as markers of hyperarousal in Gulf War illness: Evidence against a stress-related etiology

Authors: Gail D.Tillman; Clifford S.Calley; Timothy A.Green; Virginia I.Buhl; Melanie M.Biggs; Jeffrey S.Spence; Richard W.Briggs; Robert W.Haley; Michael A.Kraut; John Hart Jr.
Publication Date: August, 2012

An exaggerated response to emotional stimuli is among the many symptoms widely reported by veterans of the 1991 Persian Gulf War. These symptomologies have been attributed to damage and dysfunction associated with deployment-related exposures. We collected event-related potential data from 22 veterans meeting Haley criteria for Gulf War (GW) Syndromes 1-3 and from 8 matched GW veteran controls, who were deployed but not symptomatic, while they performed a visual three-condition oddball task where images authenticated to be associated with the 1991 Persian Gulf War were the distractor stimuli. Hyperarousal reported by ill veterans was significantly greater than that by control veterans, but this was not paralleled by higher amplitude P3a in their ERP responses to GW-related distractor stimuli. Whereas previous studies of PTSD patients have shown higher amplitude P3b responses to target stimuli that are placed amid trauma-related nontarget stimuli, ill veterans in this study showed P3b amplitudes to target stimuli - placed amid GW-related nontarget stimuli - that were significantly lower than those of the control group. Hyperarousal scores reliably predicted P3b, but not P3a, amplitudes. Although many factors may contribute to P3b amplitude differences - most notably depression and poor sleep quality, symptoms that are prevalent in the GW syndrome groups - our findings in context of previous studies on this population are consistent with the contention that dysfunction in cholinergic and dopaminergic neurotransmitter systems, and in white matter and basal ganglia may be contributing to impairments in GW veterans.

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Travel-related disseminated Penicillium marneffei infection in a renal transplant patient

Authors: J. Hart; J.R. Dyer; B.M. Clark; D.G. McLellan; S. Perera; P. Ferrari
Publication Date: September, 2012

Penicillium marneffei is a thermally dimorphic fungus that causes severe human immunodeficiency virus-related opportunistic infection in endemic areas of Southeast Asia and has rarely been reported in solid organ transplant (SOT) recipients. We report here the case of an Australian renal transplant patient who presented with disseminated P. marneffei infection shortly after a 10-day holiday to Vietnam, and review all previously published cases of penicilliosis associated with renal transplantation. This is the first reported case, to our knowledge, of P. marneffei infection in an SOT recipient acquired during travel to an endemic country, and highlights the importance of an accurate travel history when opportunistic infection is suspected, as well as giving appropriate health advice to transplant patients who travel.

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Threat as a Feature in Visual Semantic Object Memory

Authors: Clifford S. Calley; Michael A. Motes; H-Sheng Chiang; Virginia Buhl; Jeffrey S. Spence; Hervé Abdi; Raksha Anand; Mandy Maguire; Leonardo Estevez; Richard Briggs; Thomas Freeman; Michael A. Kraut; John Hart
Publication Date: December, 2011

Threatening stimuli have been found to modulate visual processes related to perception and attention. The present functional magnetic resonance imaging (fMRI) study investigated whether threat modulates visual object recognition of man-made and naturally occurring categories of stimuli. Compared with nonthreatening pictures, threatening pictures of real items elicited larger fMRI BOLD signal changes in medial visual cortices extending inferiorly into the temporo-occipital (TO) ‘‘what’’ pathways. This region elicited greater signal changes for threatening items compared to nonthreatening from both the natural-occurring and man-made stimulus supraordinate categories, demonstrating a featural component to these visual processing areas. Two additional loci of signal changes within more lateral inferior TO areas (bilateral BA18 and 19 as well as the right ventral temporal lobe) were detected for a category–feature interaction, with stronger responses to man-made (category) threatening (feature) stimuli than to natural threats. The findings are discussed in terms of visual recognition of processing efficiently or rapidly groups of items that confer an advantage for survival.

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Event-related potential patterns associated with hyperarousal in Gulf War illness syndrome groups

Authors: Gail D. Tillman; Clifford S. Calley; Timothy A. Green; Virginia I. Buhl; Melanie M. Biggs; Jeffrey S. Spence; Richard W. Briggs; Robert W. Haley; John Hart Jr.; Michael A. Kraut
Publication Date: June, 2012

An exaggerated response to emotional stimuli is one of the several symptoms widely reported by veterans of the 1991 Persian Gulf War. Many have attributed these symptoms to post-war stress; others have attributed the symptoms to deployment-related exposures and associated damage to cholinergic, dopaminergic, and white matter systems. We collected event-related potential (ERP) data from 20 veterans meeting Haley criteria for Gulf War Syndromes 1–3 and from 8 matched Gulf War veteran controls, who were deployed but not symptomatic, while they performed an auditory three-condition oddball task with gunshot and lion roar sounds as the distractor stimuli. Reports of hyperarousal from the ill veterans were significantly greater than those from the control veterans; different ERP profiles emerged to account for their hyperarousability. Syndromes 2 and 3, who have previously shown brainstem abnormalities, show significantly stronger auditory P1 amplitudes, purported to indicate compromised cholinergic inhibitory gating in the reticular activating system. Syndromes 1 and 2, who have previously shown basal ganglia dysfunction, show significantly weaker P3a response to distractor stimuli, purported to indicate dysfunction of the dopaminergic contribution to their ability to inhibit distraction by irrelevant stimuli. All three syndrome groups showed an attenuated P3b to target stimuli, which could be secondary to both cholinergic and dopaminergic contributions or disruption of white matter integrity.

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Differences in obsessional beliefs and emotion appraisal in obsessive compulsive symptom presentation

Authors: Angela H.Smith; Chad T.Wetterneck; John M.Hart; Mary B.Short; Thröstur Björgvinsson
Publication Date: November, 2011

Obsessive-compulsive disorder (OCD) is a heterogeneous condition with symptom presentation that includes contamination, harm, unacceptable thoughts, and symmetry. Researchers have begun to examine the ideographic nature of OCD symptoms to aid the development of specialized treatment approaches. Obsessional beliefs are often implicated in the development and maintenance of the disorder; however, much of the variance in symptom severity is not accounted for by these beliefs. Less attention has been paid to the role of emotions in OCD, and to date, no study has investigated beliefs about emotions (i.e., emotion appraisal) in clinical samples of OCD. In the present study, 44 participants were recruited from residential and intensive outpatient facilities and private practitioners specializing in OCD treatment. Participants completed measures of OCD severity, obsessional beliefs and emotion appraisal. Results indicated that both obsessional beliefs and emotion appraisal were correlated with each of the symptom presentations to varying degrees, and severity in each of the subtypes was predicted by a different model. Implications for cognitive and emotional conceptualizations of OCD are discussed.

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Brain activity in adolescent major depressive disorder before and after fluoxetine treatment

Authors: Rongrong Tao; Clifford S. Calley; John Hart; Taryn L. Mayes; Paul A. Nakonezny; Hanzhang Lu; Betsy D. Kennard; Carol A. Tamminga; Graham J. Emslie
Publication Date: October, 2011

Objective: Major depression in adolescents is a significant public health concern because of its frequency and severity. To examine the neurobiological basis of depression in this population, the authors studied functional activation characteristics of the brain before and after antidepressant treatment in antidepressant-naive depressed adolescents and healthy comparison subjects. Method: Depressed (N=19) and healthy (N=21) adolescents, ages 11 to 18 years, underwent functional MRI assessment while viewing fearful and neutral facial expressions at baseline and again 8 weeks later. The depressed adolescents received 8 weeks of open-label fluoxetine treatment after their baseline scan. Results: Voxel-wise whole brain analyses showed that depressed youths have exaggerated brain activation compared with healthy comparison subjects in multiple regions, including the frontal, temporal, and limbic cortices. The 8 weeks of fluoxetine treatment normalized most of these regions of hyperactivity in the depressed group. Region-of-interest analyses of the areas involved in emotion processing indicated that before treatment, depressed youths had significantly greater activations to fearful relative to neutral facial expressions than did healthy comparison subjects in the amygdala, orbitofrontal cortex, and subgenual anterior cingulate cortex bilaterally. Fluoxetine treatment decreased activations in all three regions, as compared with the repeat scans of healthy comparison subjects. Conclusions: While effective treatments are available, the impact of depression and its treatment on the brain in adolescents is understudied. This study confirms increases in brain activation in untreated depressed adolescents and demonstrates reductions in these aberrant activations with treatment.

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Automatic EEG artifact removal based on ICA and hierarchical clustering

Authors: Yuan Zou; John Hart; Roozbeh Jafari
Publication Date: March, 2012

Electroencephalography (EEG) is the recording of electrical activity along the scalp produced by the firing of neurons within the brain. These activities can be decoded by signal processing techniques, however, they are typically influenced by extraneous interference, like muscle movements, eye blinks, eye movements, background noise, etc. Therefore, a preprocessing step to remove artifacts is extremely important. This paper presents an effective artifact removal algorithm, based on Independent Component Analysis (ICA) and Hierarchical Clustering. Our technique utilizes general temporal and spectral features and particular information about target Event-Related Potentials (ERPs) (e.g. the timing of N200 and P300 on inhibition task or the specific electrodes contributing to the ERPs) to separate ERPs and artifact activities. Our method considers templates for desired ERPs to select event-related components for signal reconstruction. In our experimental study, we show that our proposed method can effectively enhance the ERPs for all fifteen subjects in the study, even for those that barely display ERPs in the raw recordings.

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Contextual effects on conceptual blending in metaphors: An event-related potential study

Authors: Fan-Pei Gloria Yang; Kailyn Bradley; Madiha Huq; Dai-Lin Wu; Daniel C. Krawczyk
Publication Date: October, 2012

Blending theory proposes that metaphor involves mappings between elements in two distinct domains and integration of information from these two domains. Previous event-related potential (ERP) studies have suggested that literal mapping occurs during metaphor comprehension. However, it has remained unclear whether accessing literal meanings affects metaphor comprehension and the contextual factors affecting blending remain poorly understood. The present study used a two stimulus word-to-sentence matching paradigm to study the effects of literal mapping and semantic congruity on metaphor comprehension using probe words from different domains. ERPs were recorded when 18 participants read short novel metaphors (e.g., The girl is a lemon) or literal control sentences (e.g., The fruit is a lemon) preceded by either a relevant or irrelevant word. Five conditions were measured: congruent target metaphor, congruent source metaphor, congruent literal, incongruent metaphor, and incongruent literal conditions. The analysis of the late positive components (LPC) revealed a significant difference in the P600 amplitudes between incongruent and congruent conditions. We also demonstrated that mapping across remote domains evoked larger P600 amplitudes than mapping across close domains or performing no mapping. The results suggest that the demands of conceptual reanalysis are associated with conceptual mapping and incongruity in both literal and metaphorical language, which supports the position of blending theory that there is a shared mechanism for both metaphoric and literal language comprehension. Amplitude differences suggest that integration difficulty is modulated by mapping degree rather than the timing of lexical access in the present study. Our results do not provide evidence that directly supports earlier models that propose literal meanings are accessed before or in parallel with metaphoric meanings.

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Tracking Cognitive Phases in Analogical Reasoning With Event-Related Potentials

Authors: Mandy J. Maguire; M. Michelle McClelland; Colin M. Donovan; Gail D. Tillman; Daniel C. Krawczyk
Publication Date: November, 2011

Analogical reasoning consists of multiple phases. Four-term analogies (A:B::C:D) have an encoding period in which the A:B pair is evaluated prior to a mapping phase. The electrophysiological timing associated with analogical reasoning has remained unclear. We used event-related potentials to identify neural timing related to analogical reasoning relative to perceptual and semantic control conditions. Spatiotemporal principal-components analyses revealed differences primarily in left frontal electrodes during encoding and mapping phases of analogies relative to the other conditions. The timing of the activity differed depending upon the phase of the problem. During the encoding of A:B terms, analogies elicited a positive deflection compared to the control conditions between 400 and 1,200 ms, but for the mapping phase analogical processing elicited a negative deflection that occurred earlier and for a shorter time period, between 350 and 625 ms. These results provide neural and behavioral evidence that 4-term analogy problems involve a highly active evaluation phase of the A:B pair.

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The cognition and neuroscience of relational reasoning

Authors: Daniel C. Krawczyk
Publication Date: December, 2010

There has been a growing interest in understanding the complex cognitive processes that give rise to human reasoning. This review focuses on the cognitive and neural characteristics of relational reasoning and analogy performance. Initially relational reasoning studies that have investigated the neural basis of abstract reasoning with an emphasis on the prefrontal cortex are described. Next studies of analogical reasoning are reviewed with insights from neuropsychological and neuroimaging studies. Additionally, studies of cognitive components in analogical reasoning are described. This review draws together insights from numerous studies and concludes that prefrontal areas exhibit domain independence in relational reasoning, while posterior areas within the temporal, parietal, and occipital lobes show evidence of domain dependence in reasoning. Lastly, future directions in the study of relational reasoning are discussed.

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Chess Masters Show a Hallmark of Face Processing With Chess

Authors: Amy L. Boggan; James C. Bartlett; Daniel C. Krawczyk
Publication Date: July, 2011

Face processing has several distinctive hallmarks that researchers have attributed either to face-specific mechanisms or to extensive experience distinguishing faces. Here, we examined the face-processing hallmark of selective attention failure—as indexed by the congruency effect in the composite paradigm—in a domain of extreme expertise: chess. Among 27 experts, we found that the congruency effect was equally strong with chessboards and faces. Further, comparing these experts with recreational players and novices, we observed a trade-off: Chess expertise was positively related to the congruency effect with chess yet negatively related to the congruency effect with faces. These and other findings reveal a case of expertise-dependent, facelike processing of objects of expertise and suggest that face and expert-chess recognition share common processes.

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Three approaches to investigating functional compromise to the default mode network after traumatic axonal injury

Authors: Ana Arenivas; Ramon Diaz-Arrastia; Jeffrey Spence; C. Munro Cullum; Kamini Krishnan; Christopher Bosworth; Carlee Culver; Beth Kennard; Carlos Marquez de la Plata
Publication Date: July, 2012

The default mode network (DMN) is a reliably elicited functional neural network with potential clinical implications. Its discriminant and prognostic utility following traumatic axonal injury (TAI) have not been previously investigated. The present study used three approaches to analyze DMN functional connectedness, including a whole-brain analysis [A1], network-specific analysis [A2], and between-node (edge) analysis [A3]. The purpose was to identify the utility of each method in distinguishing between healthy and brain-injured individuals, and determine whether observed differences have clinical significance. Restingstate fMRI was acquired from 25 patients with TAI and 17 healthy controls. Patients were scanned 6–11 months postinjury, and functional and neurocognitive outcomes were assessed the same day. Using all three approaches, TAI subjects revealed significantly weaker functional connectivity (FC) than controls, and binary logistic regressions demonstrated all three approaches have discriminant value. Clinical outcomes were not correlated with FC using any approach. Results suggest that compromise to the functional connectedness of the DMN after TAI can be identified using resting-state FC; however, the degree of functional compromise to this network, as measured in this study, may not have clinical implications in chronic TAI.

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White matter tract integrity predicts visual search performance in young and older adults

Authors: Ilana J. Bennetta; Michael A. Motesa; Neena K. Raoa; Bart Rypma
Publication Date: February, 2011

Functional imaging research has identified frontoparietal attention networks involved in visual search, with mixed evidence regarding whether different networks are engaged when the search target differs from distracters by a single (elementary) versus multiple (conjunction) features. Neural correlates of visual search, and their potential dissociation, were examined here using integrity of white matter connecting the frontoparietal networks. The effect of aging on these brain-behavior relationships was also of interest. Younger and older adults performed a visual search task and underwent diffusion tensor imaging (DTI) to reconstruct 2 frontoparietal (superior and inferior longitudinal fasciculus; SLF and ILF) and 2 midline (genu, splenium) white matter tracts. As expected, results revealed age-related declines in conjunction, but not elementary, search performance; and in ILF and genu tract integrity. Importantly, integrity of the superior longitudinal fasciculus, ILF, and genu tracts predicted search performance (conjunction and elementary), with no significant age group differences in these relationships. Thus, integrity of white matter tracts connecting frontoparietal attention networks contributes to search performance in younger and older adults.

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The Network Architecture of Cortical Processing in Visuo-spatial Reasoning

Authors: Ehsan Shokri-Kojori; Michael A. Motes; Bart Rypma; Daniel C. Krawczyk
Publication Date: May, 2012

Reasoning processes have been closely associated with prefrontal cortex (PFC), but specifically emerge from interactions among networks of brain regions. Yet it remains a challenge to integrate these brain-wide interactions in identifying the flow of processing emerging from sensory brain regions to abstract processing regions, particularly within PFC. Functional magnetic resonance imaging data were collected while participants performed a visuo-spatial reasoning task. We found increasing involvement of occipital and parietal regions together with caudal-rostral recruitment of PFC as stimulus dimensions increased. Brain-wide connectivity analysis revealed that interactions between primary visual and parietal regions predominantly influenced activity in frontal lobes. Caudal-to-rostral influences were found within left-PFC. Right-PFC showed evidence of rostral-to-caudal connectivity in addition to relatively independent influences from occipito-parietal cortices. In the context of hierarchical views of PFC organization, our results suggest that a caudal-to-rostral flow of processing may emerge within PFC in reasoning tasks with minimal top-down deductive requirements.

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Prediction of task-related BOLD fMRI with amplitude signatures of resting-state fMRI

Authors: SridharS.Kannurpatti; BartRypma; BharatB.Biswal
Publication Date: March, 2012

Blood oxygen contrast-functional magnetic resonance imaging (fMRI) signals are a convolution of neural and vascular components. Several studies indicate that task-related (T-fMRI) or resting-state (R-fMRI) responses linearly relate to hypercapnic task responses. Based on the linearity of R-fMRI and T-fMRI with hypercapnia demonstrated by different groups using different study designs, we hypothesized that R-fMRI and T-fMRI signals are governed by a common physiological mechanism and that resting-state fluctuation of amplitude (RSFA) should be linearly related to T-fMRI responses. We tested this prediction in a group of healthy younger humans where R-fMRI, T-fMRI, and hypercapnic (breath hold, BH) task measures were obtained form the same scan session during resting state and during performance of motor and BH tasks. Within individual subjects, significant linear correlations were observed between motor and BH task responses across voxels. When averaged over the whole brain, the subject-wise correlation between the motor and BH tasks showed a similar linear relationship within the group. Likewise, a significant linear correlation was observed between motor-task activity and RSFA across voxels and subjects. The linear rest–task (R–T) relationship between motor activity and RSFA suggested that R-fMRI and T-fMRI responses are governed by similar physiological mechanisms. A practical use of the R–T relationship is its potential to estimate T-fMRI responses in special populations unable to perform tasks during fMRI scanning. Using the R–T relationship determined from the first group of 12 healthy subjects, we predicted the T-fMRI responses in a second group of 7 healthy subjects. RSFA in both the lower and higher frequency ranges robustly predicted the magnitude of T-fMRI responses at the subject and voxel levels. We propose that T-fMRI responses are reliably predictable to the voxel level in situations where only R-fMRI measures are possible, and may be useful for assessing neural activity in task non-compliant clinical populations.

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Auditory Memory Distortion for Spoken Prose

Authors: Joanna L. Hutchison; Timothy L. Hubbard; Blaise Ferrandino
Publication Date: May, 2012

Observers often remember a scene as containing information that was not presented but that would have likely been located just beyond the observed boundaries of the scene. This effect is called boundary extension (BE; e.g., Intraub & Richardson, 1989). Previous studies have observed BE in memory for visual and haptic stimuli, and the present experiments examined whether BE occurred in memory for auditory stimuli (prose, music). Experiments 1 and 2 varied the amount of auditory content to be remembered. BE was not observed, but when auditory targets contained more content, boundary restriction (BR) occurred. Experiment 3 presented auditory stimuli with less content and BR also occurred. In Experiment 4, white noise was added to stimuli with less content to equalize the durations of auditory stimuli, and BR still occurred. Experiments 5 and 6 presented trained stories and popular music, and BR still occurred. This latter finding ruled out the hypothesis that the lack of BE in Experiments 1–4 reflected a lack of familiarity with the stimuli. Overall, memory for auditory content exhibited BR rather than BE, and this pattern was stronger if auditory stimuli contained more content. Implications for the understanding of general perceptual processing and directions for future research are discussed.

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Brief Report: Insight into Illness and Social Attributional Style in Asperger’s Syndrome

Authors: Nyaz Didehbani; Mujeeb U. Shad; Michelle R. Kandalaft;Tandra T. Allen; Carol A. Tamminga; Daniel C. Krawczyk; Sandra B. Chapman
Publication Date: April, 2012

A number of psychiatric illnesses have been recognized to have some level of insight deficits, including developmental disorders, such as Asperger’s Syndrome (ASP). However insight into illness has not been empirically investigated in ASP and little research has examined how individuals with ASP view their deficits. This is the first study to assess insight and the relationship between insight and externalizing bias (EB) in ASP. Participants with ASP (n = 21) and healthy controls (n = 24) were recruited. Attributional style was assessed with the internal, personal, and situational attribution questionnaire. Insight was assessed with both a clinician-administered and a selfadministered measure. Results revealed that EB was negatively correlated with insight as assessed with the clinician- administered but not the self-administered measure of insight.

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Clinical Trials: New Opportunities

Authors: Sandra Bond Chapman; Carl W. Cotman; Howard M. Fillit; Michela Gallagher; and Christopher H. van Dyck
Publication Date: May, 2012

Human cognitive aging has been too long neglected and underappreciated for its critical importance to quality of life in old age. The articles in this session present novel approaches to improving cognitive function in normal aging persons with drugs and interventions that are based on findings in epidemiology, studies in aged animals, and in vitro research. In addition, since aging is the primary risk factor for Alzheimer's disease, these studies also have implications as interventions for prevention and treatment. As a field of research, new knowledge regarding the causes and mechanisms of cognitive aging are ripe for translation into human studies, with the application of this knowledge leading the development of interventions and therapeutics for the prevention of cognitive decline in old age and Alzheimer's disease.

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Gist Reasoning Training in Cognitively Normal Seniors

Authors: Raksha Anandy; Sandra B. Chapman; Audette Rackley; Molly Keebler; Jennifer Zientz; and John Hart Jr.
Publication Date: August, 2010

Study on the impact of Gist Reasoning Training in cognitively normal seniors.

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